Faculty Profiles - YAMADA HISAKATA

Information

写真a

YAMADA HISAKATA

Organization

Faculty of Medical Sciences Department of Clinical Medicine Academic Researcher

Contact information

Tel

0926426962

Profile

education, clinilcal and basic research

External link

Degree

MD PhD

Research History

Lunds Universitet 2000.5 - 2003.10

Research Interests・Research Keywords

Research theme： Elucidating the regulatory mechanism of host defense system in health and disease.

Keyword： Immunology

Research period： 2004.4

Papers

Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5 Invited Reviewed International journal

Kusano S, Ueda S, Oryoji D, Toyoumi A, Hashimoto-Tane A, Kishi H, Hamana H, Muraguchi A, Jin H, Arase H, Miyadera H, Kishikawa R, Yoshikai Y, Yamada H, Yamamoto K, Nishimura Y, Saito T, Sasazuki T, Yokoyama S

International Immunology 2023.7

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DOI： 10.1093/intimm/dxad024
Low avidity observed for anti-citrullinated peptide antibody is not a general phenomenon for autoantibodies Invited Reviewed International journal

Yamada H, Haraguchi A, Tsuru T, Kondo M, Sagawa F, Niiro H, Nakashima Y

Annals of Rheumatic Diseases 2023.7

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DOI： 10.1136/ard-2023-224303
The Search for the Pathogenic T Cells in the Joint of Rheumatoid Arthritis: Which T-Cell Subset Drives Autoimmune Inflammation? Invited Reviewed International journal

Yamada H

International Journal of Molecular Sciences 24 ( 8 ) 6930 2023.4

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DOI： doi: 10.3390/ijms24086930
Is there a reduction in hip destruction under a treat-to-target strategy in patients with rheumatoid arthritis? Invited Reviewed International journal

Tsushima H, Takahide S, Akasaki Y, Fujiwara T, Hara D, Ikemura S, Sakuraba K, Kamura S, Miyahara H, Yamada H, Fukushi JI, Nakashima Y.

Modern Rheumatology 2023.2

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DOI： doi: 10.1093/mr/road021
Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry. Invited Reviewed International journal

Fujiwara T, Kondo M, Yamada H, Haraguchi A, Fujimura K, Sakuraba K, Kamura S, Fukushi JI, Miyahara H, Inoue Y, Tsuru T, Shuto T, Yoshizawa S, Suematsu E, Miyamura T, Ayano M, Mitoma H, Arinobu Y, Niiro H, Ohishi M, Hirata A, Tokunaga S, Takada A, Hara D, Tsushima H, Akasaki Y, Ikemura S, Sueishi T, Toya M, Sakuragi T, Tsutsui T, Kai K, Arisumi S, Nakashima Y.

Arthritis Research & Therapy 24 ( 1 ) 53 2022.2

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DOI： doi: 10.1186/s13075-022-02746-5
G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis Reviewed

Masakazu Toya, Yukio Akasaki, Takuya Sueishi, Ichiro Kurakazu, Masanari Kuwahara, Taisuke Uchida, Tomoaki Tsutsui, Hidetoshi Tsushima, Hisakata Yamada, Martin K. Lotz, Yasuharu Nakashima

Scientific Reports 11 ( 1 ) 2021.12

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<title>Abstract</title>G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had a significantly higher proportion of GRK5-positive cells in the synovial lining layer than healthy control synovium. Gene expression and NF-κB activation in lipopolysaccharide-stimulated human SW982 synovial cells were significantly suppressed by silencing of the <italic>GRK5</italic> gene. Similarly, GRK5 kinase activity inhibition in human primary RA synovial cells attenuated gene expressions of inflammatory factors. In a murine model of collagen antibody-induced arthritis, arthritis scores and serum IL6 production of <italic>GRK5</italic> knockout (GRK5^-/-) mice were significantly lower than those of wild-type mice. Histologically, the degree of synovitis and cartilage degeneration in GRK5^-/- mice was significantly lower than in wild-type mice. In in vitro analyses using activated murine macrophages and fibroblast-like synoviocytes, gene expression of inflammatory factors and p65 nuclear translocation were significantly lower in GRK5^-/- mice compared to wild-type mice. In conclusion, our results suggested that GRK5 is deeply involved in the pathogenesis of inflammatory arthritis, therefore, GRK5 inhibition could be a potential therapeutic target for types of inflammatory arthritis such as RA.

DOI： 10.1038/s41598-021-90020-0
Autoreactivity of Peripheral Helper T Cells in the Joints of Rheumatoid Arthritis Reviewed

Takahide Sakuragi, Hisakata Yamada, Akihisa Haraguchi, Kazuhiro Kai, Jun-ichi Fukushi, Satoshi Ikemura, Yukio Akasaki, Toshifumi Fujiwara, Hidetoshi Tsushima, Tomoko Tsutsui, Masakazu Kondo, Yasunobu Yoshikai, Seiji Okada, Yasuharu Nakashima

The Journal of Immunology 206 ( 9 ) 2045 - 2051 2021.5

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DOI： 10.4049/jimmunol.2000783
Adaptive immunity in the joint of rheumatoid arthritis Invited Reviewed

Hisakata Yamada

Immunological Medicine 1 - 11 2021.5

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DOI： 10.1080/25785826.2021.1930371
Human PD-1hiCD8+ T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis Reviewed

Kazuhiko Higashioka, Motoki Yoshimura, Takahide Sakuragi, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Makoto Kikukawa, Hisakata Yamada, Takahiko Horiuchi, Koichi Akashi, Hiroaki Niiro

Frontiers in Immunology 12 2021.3

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<sec><title>Background</title>Rheumatoid arthritis (RA) is a prototypical autoantibody-driven autoimmune disease in which T-B interactions play a critical role. Recent comprehensive analysis suggests that PD-1⁺CD8⁺ T cells as well as two distinct IL-21-producing PD-1⁺CD4⁺ T cell subsets, follicular helper T (Tfh) and peripheral helper T (Tph) cells, are involved in the pathogenesis of RA. Herein, we aimed to clarify a generation mechanism of IL-21-producing CD8⁺ T cells in humans, and to characterize this novel subset in patients with RA.

</sec><sec><title>Methods</title>CD8⁺ T cells in the peripheral blood (PB) and synovial fluid (SF) of healthy control (HC) and patients with RA were subject to the analysis of IL-21 mRNA and protein. We evaluated the surface marker, cytokine and transcription profiles of IL-21-producing CD8⁺ T cells in HCPB, RAPB and RASF.

</sec><sec><title>Results</title>IL-21-producing CD8⁺ T cells were enriched in the CD45RA^-(memory) PD-1⁺, especially PD-1^hi subpopulation, and IL-12 and IL-21 synergistically induced IL-21 production by naïve CD8⁺ T cells. Memory PD-1^hiCD8⁺ T cells in HCPB facilitated plasmablast differentiation and IgG production in an IL-21-dependent manner. In addition, PD-1^hiCD8⁺ T cells in RASF and RAPB produced large amounts of IL-21 and were characterized by high levels of CD28, ICOS, CD69, HLA-DR, and CCR2 but not CXCR5. Furthermore, PD-1^hiCD8⁺ T cells expressed high levels of transcripts of <italic>MAF</italic> and <italic>PRDM1</italic>, a feature observed in Tph cells.

</sec><sec><title>Conclusions</title>Identification of IL-21-producing PD-1^hiCD8⁺ T cells expands our knowledge of T cell subsets with B helper functions in RA. Selective targeting of these subsets could pave an avenue for the development of novel treatment strategies for this disease.

</sec>

DOI： 10.3389/fimmu.2021.654623
Type 1 helper T cells generate CXCL9/10-producing T-bet+ effector B cells potentially involved in the pathogenesis of rheumatoid arthritis Reviewed

Tsuyoshi Nakayama, Motoki Yoshimura, Kazuhiko Higashioka, Kohta Miyawaki, Yuri Ota, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Makoto Kikukawa, Hisakata Yamada, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro

Cellular Immunology 360 104263 - 104263 2021.2

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DOI： 10.1016/j.cellimm.2020.104263
Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes Reviewed

Kenichiro Yahiro, Yoshihiro Matsumoto, Hisakata Yamada, Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Makoto Nakagawa, Atsushi Kimura, Eijiro Shimada, Seiji Okada, Yoshinao Oda, Yasuharu Nakashima

Cancer Immunology, Immunotherapy 69 ( 5 ) 745 - 758 2020.5

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DOI： 10.1007/s00262-020-02508-9
Abatacept reduces disease activity of rheumatoid arthritis independently of modulating anti-citrullinated peptide antibody production Reviewed

Hisakata Yamada, Tomomi Tsuru, Takeshi Otsuka, Masayuki Maekawa, Hiroshi Harada, Takaaki Fukuda, Hiroshi Tsukamoto, Akira Maeyama, Shigeru Yoshizawa, Ken Wada, Yasuharu Nakashima, Eisuke Shono, Seiji Yoshizawa, Hiroshi Jojima, Masakazu Kondo

Immunological Medicine 43 ( 2 ) 87 - 91 2020.4

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DOI： 10.1080/25785826.2020.1718833
IL-7R–Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis Reviewed

Guangwei Cui, Akihiro Shimba, Guangyong Ma, Kazuhiko Takahara, Shizue Tani-ichi, Yuanbo Zhu, Takuma Asahi, Akifumi Abe, Hitoshi Miyachi, Satsuki Kitano, Takahiro Hara, Jun-ichirou Yasunaga, Hirotsugu Suwanai, Hisakata Yamada, Masao Matsuoka, Kohjiro Ueki, Yasunobu Yoshikai, Koichi Ikuta

The Journal of Immunology 204 ( 4 ) 844 - 857 2020.2

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DOI： 10.4049/jimmunol.1900456
CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines Reviewed

Ayako Takaki-Kuwahara, Yojiro Arinobu, Kohta Miyawaki, Hisakata Yamada, Hirofumi Tsuzuki, Kensuke Irino, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Hiroshi Tsukamoto, Takahiko Horiuchi, Hiroaki Niiro, Koichi Akashi

Arthritis Research & Therapy 21 ( 1 ) 2019.12

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DOI： 10.1186/s13075-019-1984-x
Drug survival rates of biological disease-modifying antirheumatic drugs and Janus kinase-inhibitor therapy in 801 rheumatoid arthritis patients: a 14 year-retrospective study from a rheumatology clinic in Japan Reviewed

Masakazu Kondo, Hisakata Yamada

Modern Rheumatology 29 ( 6 ) 928 - 935 2019.11

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DOI： 10.1080/14397595.2018.1537556
Development of a new monoclonal antibody specific to mouse Vγ6 chain Reviewed

Shinya Hatano, Xin Tun, Naoto Noguchi, Dan Yue, Hisakata Yamada, Xun Sun, Mitsuru Matsumoto, Yasunobu Yoshikai

Life Science Alliance 2 ( 3 ) e201900363 - e201900363 2019.6

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There are seven Vγ gene segments in the TCR γ chain loci of mice. We developed monoclonal antibodies (mAbs) specific to the Vγ6 chain (Heilig & Tonegawa nomenclature). By immunizing Vγ4/6 KO mice with complementarity-determining region peptides in Vγ6 chains, we generated three hybridomas. These hybridomas produced mAbs capable of cell surface staining of Vγ6/Vδ1 gene–transfected T-cell line lacking TCR as well as of Vγ1⁻ Vγ4⁻ Vγ5⁻ Vγ7⁻ γδ T cells and the CD3^high TCRδ^int γδ T cells in various organs. The location of Vγ6⁺ γδ T cells, which peaked in the newborn thymus, was associated with mTEC. In vivo administration of clone 1C10-1F7 mAb impaired protection against <italic>Klebsiella pneumoniae</italic> infection but ameliorated psoriasis-like dermatitis induced by imiquimod treatment. These new mAbs are useful to elucidate the development, location, and functions of Vγ6 γδ T cells in mice.

DOI： 10.26508/lsa.201900363
Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide–Specific Antigen Receptor Are Tolerized in Normal Conditions Reviewed

Hisakata Yamada, Tatsuhiko Ozawa, Hiroyuki Kishi, Seiji Okada, Yasuharu Nakashima, Atsushi Muraguchi, Yasunobu Yoshikai

The Journal of Immunology 201 ( 12 ) 3492 - 3496 2018.12

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DOI： 10.4049/jimmunol.1800826
T cells specific for post-translational modifications escape intrathymic tolerance induction Reviewed

Bruno Raposo, Patrick Merky, Christina Lundqvist, Hisakata Yamada, Vilma Urbonaviciute, Colin Niaudet, Johan Viljanen, Jan Kihlberg, Bruno Kyewski, Olov Ekwall, Rikard Holmdahl, Johan Bäcklund

Nature Communications 9 ( 1 ) 2018.12

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DOI： 10.1038/s41467-017-02763-y
Interleukin-21 Induces Short-Lived Effector CD8 + T Cells but Does Not Inhibit Their Exhaustion after Mycobacterium bovis BCG Infection in Mice Reviewed

Naoto Noguchi, Risa Nakamura, Shinya Hatano, Hisakata Yamada, Xun Sun, Naoya Ohara, Yasunobu Yoshikai

Infection and Immunity 86 ( 8 ) 2018.8

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Interleukin 21 (IL-21) is a pleiotropic common cytokine receptor γ chain cytokine that promotes the effector functions of NK cells and CD8
⁺
T cells and inhibits CD8
⁺
T cell exhaustion during chronic infection. We found that the absolute number of short-lived effector CD8
⁺
T cells (SLECs) (KLRG1
^high
CD127
^low
) decreased significantly in IL-21 receptor-deficient (IL-21R
^−/−
) mice during
<named-content content-type="genus-species">Mycobacterium bovis</named-content>
bacillus Calmette-Guérin (BCG) infection.

DOI： 10.1128/iai.00147-18
Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA Reviewed

Haraguchi A, Yamada H, Kondo M, Okazaki K, Fukushi JI, Oyamada A, Yoshikai Y, Nakashima Y

Clin Exp Rheumatol 36 ( 4 ) 612 - 618 2018.6

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Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis Reviewed

Atsunobu Takeda, Hisakata Yamada, Eiichi Hasegawa, Mitsuru Arima, Shoji Notomi, Sayaka Myojin, Takeru Yoshimura, Toshio Hisatomi, Hiroshi Enaida, Ryoji Yanai, Kazuhiro Kimura, Tatsuro Ishibashi, Koh-Hei Sonoda

Japanese Journal of Ophthalmology 62 ( 3 ) 398 - 406 2018.5

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DOI： 10.1007/s10384-018-0587-4
Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4 Reviewed

Akihiro Shimba, Guangwei Cui, Shizue Tani-ichi, Makoto Ogawa, Shinya Abe, Fumie Okazaki, Satsuki Kitano, Hitoshi Miyachi, Hisakata Yamada, Takahiro Hara, Yasunobu Yoshikai, Takashi Nagasawa, Günther Schütz, Koichi Ikuta

Immunity 48 ( 2 ) 286 - 298.e6 2018.2

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DOI： 10.1016/j.immuni.2018.01.004
CD5 − NK1.1 + γδ T Cells that Develop in a Bcl11b-Independent Manner Participate in Early Protection against Infection Reviewed

Shinya Hatano, Tesshin Murakami, Naoto Noguchi, Hisakata Yamada, Yasunobu Yoshikai

Cell Reports 21 ( 5 ) 1191 - 1202 2017.10

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DOI： 10.1016/j.celrep.2017.10.007
Minimum 10-year results of cementless total hip arthroplasty in patients with rheumatoid arthritis Reviewed

Akihisa Haraguchi, Yasuharu Nakashima, Hisaaki Miyahara, Yukio Esaki, Ken Okazaki, Jun-ichi Fukushi, Go Hirata, Satoshi Ikemura, Satoshi Kamura, Koji Sakuraba, Kenjiro Fujimura, Yukio Akasaki, Hisakata Yamada

Modern Rheumatology 27 ( 4 ) 598 - 604 2017.7

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DOI： 10.1080/14397595.2016.1256024
Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis Reviewed

Hisakata Yamada, Akihisa Haraguchi, Koji Sakuraba, Ken Okazaki, Jun-Ichi Fukushi, Hideki Mizu-Uchi, Yukio Akasaki, Yukio Esaki, Satoshi Kamura, Kenjiro Fujimura, Masakazu Kondo, Hisaaki Miyahara, Yasuharu Nakashima, Yasunobu Yoshikai

RMD Open 3 ( 1 ) e000487 - e000487 2017.7

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DOI： 10.1136/rmdopen-2017-000487
Generation mechanism of RANKL+ effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis Reviewed

Yuri Ota, Hiroaki Niiro, Shun-ichiro Ota, Naoko Ueki, Hirofumi Tsuzuki, Tsuyoshi Nakayama, Koji Mishima, Kazuhiko Higashioka, Siamak Jabbarzadeh-Tabrizi, Hiroki Mitoma, Mitsuteru Akahoshi, Yojiro Arinobu, Akiko Kukita, Hisakata Yamada, Hiroshi Tsukamoto, Koichi Akashi

Arthritis Research & Therapy 18 ( 1 ) 2016.12

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DOI： 10.1186/s13075-016-0957-6
Two Types of Interleukin 17A–Producing γδ T Cells in Protection Against Pulmonary Infection WithKlebsiella pneumoniae Reviewed

Tesshin Murakami, Shinya Hatano, Hisakata Yamada, Yoichiro Iwakura, Yasunobu Yoshikai

Journal of Infectious Diseases 214 ( 11 ) 1752 - 1761 2016.12

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DOI： 10.1093/infdis/jiw443
Interleukin-21 signaling in B cells, but not in T cells, is indispensable for the development of collagen-induced arthritis in mice Reviewed

Koji Sakuraba, Akiko Oyamada, Kenjiro Fujimura, Rosanne Spolski, Yukihide Iwamoto, Warren J. Leonard, Yasunobu Yoshikai, Hisakata Yamada

Arthritis Research & Therapy 18 ( 1 ) 2016.12

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DOI： 10.1186/s13075-016-1086-y
Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer Reviewed

Ario Takeuchi, Masatoshi Eto, Katsunori Tatsugami, Masaki Shiota, Hisakata Yamada, Yoriyuki Kamiryo, Takashi Dejima, Eiji Kashiwagi, Keijiro Kiyoshima, Junichi Inokuchi, Ryosuke Takahashi, Akira Yokomizo, Naoya Ohara, Yasunobu Yoshikai

International Immunopharmacology 35 327 - 331 2016.6

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DOI： 10.1016/j.intimp.2016.03.007
Delayed diagnosis of ankylosing spondylitis in a Japanese population Reviewed

Yasuharu Nakashima, Masanobu Ohishi, Ken Okazaki, Jun-Ichi Fukushi, Akiko Oyamada, Daisuke Hara, Toshio Doi, Yukio Akasaki, Hisakata Yamada, Yukihide Iwamoto

Modern Rheumatology 26 ( 3 ) 421 - 425 2016.5

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DOI： 10.3109/14397595.2015.1088679
Outcome of Joint-Preserving Arthroplasty for Rheumatoid Forefoot Deformities Reviewed

Jun-ichi Fukushi, Yasuharu Nakashima, Ken Okazaki, Hisakata Yamada, Taro Mawatari, Masanobu Ohishi, Akiko Oyamada, Yukio Akasaki, Yukihide Iwamoto

Foot & Ankle International 37 ( 3 ) 262 - 268 2016.3

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<sec><title>Background:</title> Along with the recent advances in the pharmacological management of rheumatoid arthritis, there is a trend toward the use of joint-preserving surgery in the treatment of rheumatoid forefoot deformities. However, the clinical outcomes of joint-preserving surgery for rheumatoid forefoot deformities have not been assessed in comparison to resection arthroplasty.

</sec><sec><title>Methods:</title> We retrospectively evaluated 23 feet in 17 patients with rheumatoid forefoot deformities who underwent surgery between January 2010 and December 2013. The patients included 1 male (1 foot) and 16 females (22 feet), with a mean age of 62 years. The mean length of follow-up was 28 months. The patients were treated by 3 surgeons. One surgeon performed joint-preserving procedures (JP group) to the feet in which (1) no pain with motion existed, and (2) the range of motion in the first metatarsophalangeal (MTP) joint was greater than 30 degrees (n = 10); otherwise, resection arthroplasty with arthrodesis of the first MTP joint was performed (n = 3). The other surgeons performed resection arthroplasty in all cases (n = 10) (RA group, n = 13 in total). The clinical outcomes of the patients were evaluated using the Japanese Society for Surgery of the Foot (JSSF) hallux and lesser toe scales.

</sec><sec><title>Results:</title> There were no significant differences in the preoperative total JSSF scores for either the hallux (54.5 and 61.4 points) or the lesser toe (45.2 and 57.4 points) between the RA and JP groups, respectively. Postoperatively, the total JSSF scores for both the hallux (79.4 and 88.2 points) and lesser toes (73.6 and 87.7 points) showed significant improvement in both the RA and JP groups, respectively; however, the JP group showed a greater postoperative improvement. The scores relating to the function category on the hallux scale and the alignment category on the lesser toe scale were significantly higher in the JP group.

</sec><sec><title>Conclusion:</title> With regard to the function of the hallux and the alignment of the lesser toes, the joint-preserving procedures for rheumatoid forefoot deformities resulted in better clinical outcomes than resection arthroplasty.

</sec><sec><title>Level of Evidence:</title> Level III, comparative case series.

</sec>

DOI： 10.1177/1071100715609981
Requirement of CD30 expression on CD4 T cells in the pathogenesis of experimental autoimmune encephalomyelitis Reviewed

Koji Shinoda, Xun Sun, Akiko Oyamada, Hisakata Yamada, Jun-ichi Kira, Yasunobu Yoshikai

Journal of Neuroimmunology 291 39 - 45 2016.2

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DOI： 10.1016/j.jneuroim.2015.12.005
Prevalence of dyslipidemia in Japanese patients with rheumatoid arthritis and effects of atorvastatin treatment Reviewed

Mio Akiyama, Taro Mawatari, Yasuharu Nakashima, Hisaaki Miyahara, Hisakata Yamada, Ken Okazaki, Jun-ichi Fukushi, Masakazu Kondo, Junji Kishimoto, Chinami Hashimura, Yukihide Iwamoto

Clinical Rheumatology 34 ( 11 ) 1867 - 1875 2015.11

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DOI： 10.1007/s10067-015-3049-0
Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes Reviewed

Kenichi Izumi, Keiichiro Mine, Yoshitaka Inoue, Miho Teshima, Shuichiro Ogawa, Yuji Kai, Toshinobu Kurafuji, Kanako Hirakawa, Daiki Miyakawa, Haruka Ikeda, Akari Inada, Manami Hara, Hisakata Yamada, Koichi Akashi, Yoshiyuki Niho, Keisuke Ina, Takashi Kobayashi, Yasunobu Yoshikai, Keizo Anzai, Teruo Yamashita, Hiroko Minagawa, Shuji Fujimoto, Hironori Kurisaki, Kazuya Shimoda, Hitoshi Katsuta, Seiho Nagafuchi

Nature Communications 6 ( 1 ) 2015.11

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DOI： 10.1038/ncomms7748
An Enhancer of the IL-7 Receptor α-Chain Locus Controls IL-7 Receptor Expression and Maintenance of Peripheral T Cells Reviewed

Akifumi Abe, Shizue Tani-ichi, Soichiro Shitara, Guangwei Cui, Hisataka Yamada, Hitoshi Miyachi, Satsuki Kitano, Takahiro Hara, Ryo Abe, Yasunobu Yoshikai, Koichi Ikuta

The Journal of Immunology 195 ( 7 ) 3129 - 3138 2015.10

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DOI： 10.4049/jimmunol.1302447
Brief Report: Successful In Vitro Culture of Rheumatoid Arthritis Synovial Tissue Explants at the Air-Liquid Interface Reviewed

Koji Sakuraba, Kenjiro Fujimura, Yasuharu Nakashima, Ken Okazaki, Jun-ichi Fukushi, Masanobu Ohishi, Akiko Oyamada, Yukio Esaki, Hisaaki Miyahara, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

Arthritis & Rheumatology 67 ( 4 ) 887 - 892 2015.4

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DOI： 10.1002/art.39019
Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation Reviewed

Ario Takeuchi, Masatoshi Eto, Katsunori Tatsugami, Hisakata Yamada, Akira Yokomizo, Masaki Shiota, Momoe Itsumi, Junichi Inokuchi, Keijiro Kiyoshima, Takashi Dejima, Kenjiro Imada, Seiji Naito, Yasunobu Yoshikai

Transplant Immunology 32 ( 2 ) 131 - 139 2015.3

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DOI： 10.1016/j.trim.2014.12.001
CD30 ligand is a new therapeutic target for central nervous system autoimmunity Reviewed

Koji Shinoda, Xun Sun, Akiko Oyamada, Hisakata Yamada, Hiromi Muta, Eckhard R. Podack, Jun-ichi Kira, Yasunobu Yoshikai

Journal of Autoimmunity 57 14 - 23 2015.2

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DOI： 10.1016/j.jaut.2014.11.005
A Genome-Wide Analysis Identifies a Notch–RBP-Jκ–IL-7Rα Axis That Controls IL-17–Producing γδ T Cell Homeostasis in Mice Reviewed

Masataka Nakamura, Kensuke Shibata, Shinya Hatano, Tetsuya Sato, Yasuyuki Ohkawa, Hisakata Yamada, Koichi Ikuta, Yasunobu Yoshikai

The Journal of Immunology 194 ( 1 ) 243 - 251 2015.1

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DOI： 10.4049/jimmunol.1401619
EBI3 is pivotal for the initiation of experimental autoimmune uveitis Reviewed

Atsunobu Takeda, Eiichi Hasegawa, Takako Fukuhara, Sayaka Hirakawa, Hisakata Yamada, Yang Yang, Takeru Yoshimura, Toshio Hisatomi, Yuji Oshima, Hiroki Yoshida, Koh-Hei Sonoda, Tatsuro Ishibashi

Experimental Eye Research 125 107 - 113 2014.8

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DOI： 10.1016/j.exer.2014.06.004
Tyk2-Dependent Bystander Activation of Conventional and Nonconventional Th1 Cell Subsets Contributes to Innate Host Defense againstListeria monocytogenesInfection Reviewed

Tomomitsu Hashiguchi, Akiko Oyamada, Koji Sakuraba, Kazuya Shimoda, Keiichi I. Nakayama, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

The Journal of Immunology 192 ( 10 ) 4739 - 4747 2014.5

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DOI： 10.4049/jimmunol.1303067
IFN-γ–Producing and IL-17–Producing γδ T Cells Differentiate at Distinct Developmental Stages in Murine Fetal Thymus Reviewed International journal

Kensuke Shibata, Hisakata Yamada, Masataka Nakamura, Shinya Hatano, Yoshinori Katsuragi, Ryo Kominami, Yasunobu Yoshikai

The Journal of Immunology 192 ( 5 ) 2210 - 2218 2014.3

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γδ T cells develop at the double-negative (DN) 2 and DN3 stages and acquire functions to produce IL-17 and IFN-γ in fetal thymus. However, the relationship between differentiation stages and their functions was unclear. In this study, we found that, although IFN-γ-producing and IL-17-producing γδ T cells developed from DN2 cells, only IFN-γ-producing γδ T cells developed from DN3 cells, indicating the direct generation of IL-17-producing γδ T cells from the DN2 stage, not through the DN3 stage. Single-cell analysis revealed that DN2 cells contained heterogeneous γδ T cell precursors with or without an ability to develop IL-17 producers. Inactivation of B cell leukemia/lymphoma 11b, a zinc finger transcription factor responsible for transition from early to late stages of DN2 cells, completely abrogated the development of IL-17-producing γδ T cells, although a unique subset of IFN-γ-producing γδ T cells expressing a high level of promyelocytic leukemia zinc finger was able to develop. Thus, our results reveal that γδ T cells are functionally differentiated to IFN-γ and IL-17 producers at different developmental stages in fetal thymus.

DOI： 10.4049/jimmunol.1302145
Identification of Independent Susceptible and Protective HLA Alleles in Japanese Autoimmune Thyroid Disease and Their Epistasis Reviewed

Sho Ueda, Daisuke Oryoji, Ken Yamamoto, Jaeduk Yoshimura Noh, Ken Okamura, Mitsuhiko Noda, Koichi Kashiwase, Yuka Kosuga, Kenichi Sekiya, Kaori Inoue, Hisakata Yamada, Akiko Oyamada, Yasuharu Nishimura, Yasunobu Yoshikai, Koichi Ito, Takehiko Sasazuki

The Journal of Clinical Endocrinology & Metabolism 99 ( 2 ) E379 - E383 2014.2

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<sec>
<title>Background:</title>
Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto thyroiditis (HT), which partially share immunological features. Determining the genetic basis that distinguishes GD and HT is a key to understanding the differences between these 2 related diseases.

</sec>
<sec>
<title>Aim:</title>
The aims of this study were to identify HLA antigens that can explain the immunopathological difference between GD and HT and to elucidate epistatic interactions between protective and susceptible HLA alleles, which can delineate the distinct function of HLA in AITD etiology.

</sec>
<sec>
<title>Design:</title>
We genotyped 991 patients with AITD (547 patients with GD and 444 patients with HT) and 481 control subjects at the HLA-A, HLA-C, HLA-B, DRB1, DQB1, and DPB1 loci. A direct comparison of HLA antigen frequencies between GD and HT was performed. We further analyzed an epistatic interaction between the susceptible and protective HLA alleles in the development of GD and HT.

</sec>
<sec>
<title>Results:</title>
We identified 4 and 2 susceptible HLA molecules primarily associated with GD and HT, respectively, HLA-B*35:01, HLA-B*46:01, HLA-DRB1*14:03, and HLA-DPB1*05:01 for GD and HLA-A*02:07 and HLA-DRB4 for HT. In a direct comparison between GD and HT, we identified GD-specific susceptible class II molecules, HLA-DP5 (HLA-DPB1*05:01; Pc = 1.0 × 10−9) and HLA-DR14 (HLA-DRB*14:03; Pc = .0018). In contrast, HLA components on 3 common haplotypes in Japanese showed significant protective effects against the development of GD and HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and HT). Interestingly, the representative protective HLA, HLA-DR13 (HLA-DRB1*13:02), was epistatic to susceptible HLA-DP5 in controlling the development of GD.

</sec>
<sec>
<title>Conclusion:</title>
We show that HLA exerts a dual function, susceptibility and resistance, in controlling the development of GD and HT. We also show that the protective HLA allele is partially epistatic to the susceptible HLA allele in GD.

</sec>

DOI： 10.1210/jc.2013-2841
Type I Interferon Plays Opposing Roles in Cytotoxicity and Interferon-γ Production by Natural Killer and CD8 T Cells after Influenza A Virus Infection in Mice.

Arimori Y, Nakamura R, YAMADA H, Shibata K, Maeda N, Kase T, Yoshikai Y

J Innate Immun. 2014 Jan 10 2014.1

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A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice Reviewed International journal

Takashi Dejima, Kensuke Shibata, Hisakata Yamada, Ario Takeuchi, Hiromitsu Hara, Masatoshi Eto, Seiji Naito, Yasunobu Yoshikai

Microbiology and Immunology 57 ( 12 ) 833 - 841 2013.12

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Hemorrhagic cystitis often arises after cyclophosphamide (CYP) administration. As yet, however, the mechanism involved in its pathogenesis is unknown. In this study, it was found that the Fc receptor γ chain (FcRγ)- caspase recruitment domain-containing protein 9 (CARD9)-dependent pathway rather than the myeloid differentiation primary response gene 88 (MyD88)-dependent pathway is involved in the pathogenesis of acute CYP-induced cystitis in mice. Rapid and transient production of interleukin (IL)-6 and IL-1β was detected in the bladder at 4 hr, preceding IL-23 and IL-17A production and an influx of neutrophils, which reached a peak at 24 hr after injection. As assessed by weight, edema and neutrophil infiltration, cystitis was significantly attenuated in CARD9 knockout (KO) and FcRγKO mice, this attenuation being accompanied by impaired production of IL-1β, IL-6, IL-23 and IL-17A. The major source of IL-17A is the vesical γδ T cell population: IL-17AKO, CδKO and Tyk2KO mice showed little IL-17A production and reduced neutrophil infiltration in the bladder after CYP injection. These results suggest that FcRγ-CARD9-dependent production of proinflammatory cytokines such as IL-1β, IL-6, and IL-23 and the subsequent activation of IL-17A-producing γδ T cells are at least partly involved in the pathogenesis of acute CYP-induced cystitis in mice.

DOI： 10.1111/1348-0421.12100
Effects of adalimumab administration in bio-naïve and bio-switch rheumatoid arthritis patients in daily clinical practice : two-year results from single center.

Tashiro Y, Yasuharu Nakashima, Okazaki K, Mawatari T, Fukushi J, Ohishi M, Oyamada A,, YAMADA H, Iwamoto Y

Fukuoka Igaku Zasshi. 2013 Nov;104(11): 2013.11

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CD30L/CD30 is critical for maintenance of IL-17A-producing γδ T cells bearing Vγ6 in mucosa-associated tissues in mice Reviewed

X Sun, K Shibata, H Yamada, Y Guo, H Muta, E R Podack, Y Yoshikai

Mucosal Immunology 6 ( 6 ) 1191 - 1201 2013.11

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DOI： 10.1038/mi.2013.18
CD30 Is Required for Activation of a Unique Subset of Interleukin-17A-Producing γδ T Cells in Innate Immunity against Mycobacterium bovis Bacillus Calmette-Guérin Infection Reviewed International journal

Ying Guo, Xun Sun, Kensuke Shibata, Hisakata Yamada, Hiromi Muta, Eckhard R. Podack, Yasunobu Yoshikai

Infection and Immunity 81 ( 10 ) 3923 - 3934 2013.10

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<title>ABSTRACT</title>Interleukin-17A (IL-17A)-producing γδ T cells are known to be activated following<named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Mycobacterium bovis</named-content>bacillus Calmette-Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing γδ T cells after BCG infection. Vγ1⁻Vγ4⁻γδ T cells preferentially expressing Vγ6/Vδ1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The number of IL-17A-producing Vγ1⁻Vγ4⁻γδ T cells bearing Vγ6 increased in peritoneal exudate cells (PEC) of wild-type (WT) mice but not in those of CD30 knockout (KO) mice in response to BCG infection. Consistently, CD30 ligand (CD30L) or CD30 expression, predominantly by Vγ1⁻Vγ4⁻γδ T cells, was rapidly upregulated after BCG infection. Inhibition of CD30L/CD30 signaling by<italic>in vivo</italic>administration of a soluble CD30 and immunoglobulin fusion protein (CD30-Ig) severely impaired activation of IL-17A-producing Vγ1⁻Vγ4⁻γδ T cells in WT mice, while stimulating CD30L/CD30 signaling by<italic>in vivo</italic>administration of agonistic anti-CD30 monoclonal antibody (MAb) restored IL-17A production by Vγ1⁻Vγ4⁻γδ T cells in CD30L KO mice after BCG infection. These results suggest that CD30 signaling plays an important role in the activation of IL-17A-producing Vγ1⁻Vγ4⁻γδ T cells bearing Vγ6 at an early stage of BCG infection.

DOI： 10.1128/iai.00887-13
Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice Reviewed International journal

Yojiro Arimori, Risa Nakamura, Hisakata Yamada, Kensuke Shibata, Naoyoshi Maeda, Tetsuo Kase, Yasunobu Yoshikai

Antiviral Research 99 ( 3 ) 230 - 237 2013.9

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Antiviral immune responses play as a double edged sword in resolution of infection and pathogenesis of acute lung injury caused by infection with highly pathogenic influenza A viruses. Here we show that type I interferons (IFNs) are important in protection against acute influenza A virus infection not only via their antiviral activity but also via their anti-inflammatory activity. IFN α receptor (IFNAR) knock-out (KO) mice exhibited increased mortality and morbidity with higher viral load after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) compared with wild-type (WT) mice, though the viruses were finally eliminated in both groups. The levels of proinflammatory cytokines in the lungs were significantly higher, while the level of IL-10 in the lungs was significantly lower in IFNAR KO mice than in WT mice during the course of infection. Restoration of IL-10 during an ongoing virus infection significantly reduced the levels of proinflammatory cytokines and improved mortality of IFNAR KO mice. These results suggest that type I IFNs are responsible not only for direct resolution of viral load but also for suppression of immunopathology caused by influenza A virus through IL-10 production.

DOI： 10.1016/j.antiviral.2013.05.007
CD4 T cell-intrinsic IL-2 signaling differentially affects Th1 and Th17 development Reviewed

Kenjiro Fujimura, Akiko Oyamada, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

Journal of Leukocyte Biology 94 ( 2 ) 271 - 279 2013.8

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DOI： 10.1189/jlb.1112581
Positive selection of self-antigen-specific CD8+T cells by hematopoietic cells Reviewed International journal

Hisakata Yamada, Kensuke Shibata, Koji Sakuraba, Kenjiro Fujimura, Yasunobu Yoshikai

European Journal of Immunology 43 ( 8 ) 2033 - 2042 2013.8

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In contrast to thymic epithelial cells, which induce the positive selection of conventional CD8(+) T cells, hematopoietic cells (HCs) select innate CD8(+) T cells whose Ag specificity is not fully understood. Here we show that CD8(+) T cells expressing an H-Y Ag-specific Tg TCR were able to develop in mice in which only HCs expressed MHC class I, when HCs also expressed the H-Y Ag. These HC-selected self-specific CD8(+) T cells resemble innate CD8(+) T cells in WT mice in terms of the expression of memory markers and effector functions, but are phenotypically distinct from the thymus-independent CD8(+) T-cell population. The peripheral maintenance of H-Y-specific CD8(+) T cells required presentation of the self-Ag and IL-15 on HCs. HC-selected CD8(+) T cells in mice lacking the Tg TCR also showed these features. Furthermore, by using MHC class I tetramers with a male Ag peptide, we found that self-Ag-specific CD8(+) T cells in TCR non-Tg mice could develop via HC-induced positive selection, supporting results obtained from H-Y TCR Tg mice. These findings indicate the presence of self-specific CD8(+) T cells that are positively selected by HCs in the peripheral T-cell repertoire.

DOI： 10.1002/eji.201242957
C-type Lectin MCL Is an FcRγ-Coupled Receptor that Mediates the Adjuvanticity of Mycobacterial Cord Factor Reviewed

Yasunobu Miyake, Kenji Toyonaga, Daiki Mori, Shigeru Kakuta, Yoshihiko Hoshino, Akiko Oyamada, Hisakata Yamada, Ken-ichiro Ono, Mikita Suyama, Yoichiro Iwakura, Yasunobu Yoshikai, Sho Yamasaki

Immunity 38 ( 5 ) 1050 - 1062 2013.5

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DOI： 10.1016/j.immuni.2013.03.010
Ly6C+Ly6G−Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury Reviewed

Hirokazu Saiwai, Hiromi Kumamaru, Yasuyuki Ohkawa, Kensuke Kubota, Kazu Kobayakawa, Hisakata Yamada, Takehiko Yokomizo, Yukihide Iwamoto, Seiji Okada

Journal of Neurochemistry 125 ( 1 ) 74 - 88 2013.4

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DOI： 10.1111/jnc.12135
Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma Reviewed

Y Fujiwara-Okada, Y Matsumoto, J Fukushi, N Setsu, S Matsuura, S Kamura, T Fujiwara, K Iida, M Hatano, A Nabeshima, H Yamada, M Ono, Y Oda, Y Iwamoto

British Journal of Cancer 108 ( 4 ) 836 - 847 2013.3

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DOI： 10.1038/bjc.2012.579
Naturally Occurring PD-1+ Memory Phenotype CD8 T Cells Belong to Nonconventional CD8 T Cells and Are Cyclophosphamide-Sensitive Regulatory T Cells Reviewed International journal

Koji Sakuraba, Kensuke Shibata, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

The Journal of Immunology 190 ( 4 ) 1560 - 1566 2013.2

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CD8 T cells expressing memory markers exist in naive mice and are thought to be of heterogeneous origin. It was recently reported that among such memory-phenotype (MP) CD8 T cells in naive mice, those expressing programmed death-1 (PD-1) had immune regulatory activity, but their origin and relationship with other regulatory CD8 T cell subsets remain unclear. In the current study, we examined detailed characteristics and functions of PD-1(+) MP CD8 T cells in naive mice. Their expression pattern of surface molecules resembled that of exhausted CD8 T cells seen in chronic viral infection. However, PD-1(+) MP CD8 T cells were detected from neonatal periods, even in the thymus; thus, they are naturally occurring. By analyzing bone marrow chimera mice in which β(2)-microglobulin-deficient mice were used as the recipients, it was revealed that PD-1(+) MP CD8 T cells were positively selected by hematopoietic cells, indicating that they belong to nonconventional CD8 T cells. However, in contrast to majority of MP CD8 T cells, PD-1(+) MP CD8 T cells were IL-15 independent. PD-1(+) MP CD8 T cells showed the fastest cell cycling among various T cell subsets in naive mice, which was consistent with the highest sensitivity to cyclophosphamide (CP) treatment. Importantly, PD-1(+) MP CD8 T cells were able to suppress delayed-type hypersensitivity response that was augmented by CP treatment. Taken together, our data indicate that the naturally occurring PD-1(+) MP CD8 T cells in naive mice are a unique subset of nonconventional CD8 T cells and represent the CP-sensitive suppressor CD8 T cells.

DOI： 10.4049/jimmunol.1202464
Evaluation of cartilage degradation in arthritis using T1ρ magnetic resonance imaging mapping Reviewed

Hidetoshi Tsushima, Ken Okazaki, Yukihisa Takayama, Masamitsu Hatakenaka, Hiroshi Honda, Toshiaki Izawa, Yasuharu Nakashima, Hisakata Yamada, Yukihide Iwamoto

Rheumatology International 32 ( 9 ) 2867 - 2875 2012.9

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DOI： 10.1007/s00296-011-2140-3
Age-related differences in cellular and molecular profiles of inflammatory responses after spinal cord injury Reviewed

Hiromi Kumamaru, Hirokazu Saiwai, Yasuyuki Ohkawa, Hisakata Yamada, Yukihide Iwamoto, Seiji Okada

Journal of Cellular Physiology 227 ( 4 ) 1335 - 1346 2012.4

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DOI： 10.1002/jcp.22845
Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells Reviewed

Hiromi Kumamaru, Yasuyuki Ohkawa, Hirokazu Saiwai, Hisakata Yamada, Kensuke Kubota, Kazu Kobayakawa, Koichi Akashi, Hideyuki Okano, Yukihide Iwamoto, Seiji Okada

Nature Communications 3 ( 1 ) 2012.1

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DOI： 10.1038/ncomms2132
A reduction of recipient regulatory T cells by cyclophosphamide contributes to an anti-tumor effect of nonmyeloablative allogeneic stem cell transplantation in mice Reviewed

Ario Takeuchi, Masatoshi Eto, Hisakata Yamada, Katsunori Tatsugami, Seiji Naito, Yasunobu Yoshikai

International Journal of Cancer 130 ( 2 ) 365 - 376 2012.1

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DOI： 10.1002/ijc.26009
Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice Reviewed

Takashi Dejima, Kensuke Shibata, Hisakata Yamada, Hiromitsu Hara, Yoichiro Iwakura, Seiji Naito, Yasunobu Yoshikai

Infection and Immunity 79 ( 11 ) 4503 - 4510 2011.11

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<title>ABSTRACT</title>

Interleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection with
<named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Candida albicans.</named-content>
Selective depletion of neutrophils by
<italic>in vivo</italic>
administration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection with
<named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. albicans.</named-content>
Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense against
<named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">C. albicans</named-content>
infection.

DOI： 10.1128/iai.05799-11
The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in mice Reviewed

Takafumi Fuchiwaki, Xun Sun, Kenjiro Fujimura, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Eckhard R. Podack, Hideyuki Kawauchi, Yasunobu Yoshikai

European Journal of Immunology 41 ( 10 ) 2947 - 2954 2011.10

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DOI： 10.1002/eji.201141423
Innate memory phenotype CD4+ T cells play a role in early protection against infection by Listeria monocytogenes in a CD30L-dependent manner Reviewed

Kenji Umeda, Xun Sun, Ying Guo, Hisakata Yamada, Kensuke Shibata, Yasunobu Yoshikai

Microbiology and Immunology 55 ( 9 ) 645 - 656 2011.9

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DOI： 10.1111/j.1348-0421.2011.00362.x
Macrophage Infiltration Predicts a Poor Prognosis for Human Ewing Sarcoma Reviewed

Toshifumi Fujiwara, Jun-ichi Fukushi, Shunsaku Yamamoto, Yoshihiro Matsumoto, Nokitaka Setsu, Yoshinao Oda, Hisakata Yamada, Seiji Okada, Kosuke Watari, Mayumi Ono, Michihiko Kuwano, Satoshi Kamura, Keiichiro Iida, Yuko Okada, Mihoko Koga, Yukihide Iwamoto

The American Journal of Pathology 179 ( 3 ) 1157 - 1170 2011.9

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DOI： 10.1016/j.ajpath.2011.05.034
Preferential Accumulation of Activated Th1 Cells Not Only in Rheumatoid Arthritis But Also in Osteoarthritis Joints Reviewed

HISAKATA YAMADA, YASUHARU NAKASHIMA, KEN OKAZAKI, TARO MAWATARI, JUN-ICHI FUKUSHI, AKIKO OYAMADA, KENJIRO FUJIMURA, YUKIHIDE IWAMOTO, YASUNOBU YOSHIKAI

The Journal of Rheumatology 38 ( 8 ) 1569 - 1575 2011.8

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<sec><title>Objective.</title>It was previously found that Th1 but not Th17 cells were predominant in the joints of rheumatoid arthritis (RA). To verify whether this is a unique feature of CD4 T cells in RA joints, we performed comparative flow cytometric analysis of CD4 T cells in RA and osteoarthritis (OA) joints.

</sec><sec><title>Methods.</title>Mononuclear cells were isolated from peripheral blood (PB), synovial membrane (SM), and synovial fluid (SF) from a total of 18 RA and 12 OA patients. The expression of surface molecules and cytokine production of CD4 T cells was examined by a flow cytometer.

</sec><sec><title>Results.</title>Most CD4 T cells in RA joints expressed memory/activation markers, such as CD45RO, HLA-DR, and CD69. CCR5 was highly expressed on CD4 T cells in SF but not in PB or SM. With regard to Th17-related molecules, CD4 T cells expressing CCR6 were not enriched in either SF or SM. In contrast, CD161-positive cells were abundant in the joint, many of which, however, produced interferon-γ but not interleukin 17A. Virtually all T cells in OA joints, although much less numerous than in RA joints, expressed activation markers. Th1 cells were predominant in both OA and RA joints, while there were a few Th17 cells. The frequency of Th17 cells in the joint tended to be lower in OA than RA.

</sec><sec><title>Conclusion.</title>There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.

</sec>

DOI： 10.3899/jrheum.101355
Notch-Hes1 pathway is required for the development of IL-17–producing γδ T cells Reviewed

Kensuke Shibata, Hisakata Yamada, Tetsuya Sato, Takashi Dejima, Masataka Nakamura, Tomokatsu Ikawa, Hiromitsu Hara, Sho Yamasaki, Ryoichiro Kageyama, Yoichiro Iwakura, Hiroshi Kawamoto, Hiroyuki Toh, Yasunobu Yoshikai

Blood 118 ( 3 ) 586 - 593 2011.7

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<title>Abstract</title>
Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17–producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17–producing γδ T cells. Hes1 is critically involved in the development of IL-17–producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)–expressing stromal cells support the development of IL-17–producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17–producing γδ T cells.

DOI： 10.1182/blood-2011-02-334995
IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer

Ario Takeuchi, Takashi Dejima, Hisakata Yamada, Kensuke Shibata, Risa Nakamura, Masatoshi Eto, Tatsuya Nakatani, Seiji Naito, Yasunobu Yoshikai

European Journal of Immunology 41 ( 1 ) 246 - 251 2011.1

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DOI： 10.1002/eji.201040773
CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses Reviewed

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard R. Podack, Yoichiro Iwakura, Yasunobu Yoshikai

The Journal of Immunology 185 ( 12 ) 7671 - 7680 2010.12

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DOI： 10.4049/jimmunol.1002229
Mechanism of Synergistic Antitumor Effect of Sorafenib and Interferon-α on Treatment of Renal Cell Carcinoma Reviewed

Ario Takeuchi, Masatoshi Eto, Katsunori Tatsugami, Hisakata Yamada, Toshihiro Oki, Keijiro Kiyoshima, Yasunobu Yoshikai, Seiji Naito

Journal of Urology 184 ( 6 ) 2549 - 2556 2010.12

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DOI： 10.1016/j.juro.2010.07.033
CD30 Ligand/CD30 Plays a Critical Role in Th17 Differentiation in Mice Reviewed

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard R. Podack, Yasunobu Yoshikai

The Journal of Immunology 185 ( 4 ) 2222 - 2230 2010.8

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DOI： 10.4049/jimmunol.1000024
Current perspectives on the role of IL-17 in autoimmune disease Invited Reviewed

Hisakata Yamada

Journal of Inflammation Research 33 - 33 2010.6

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DOI： 10.2147/jir.s6375
Interleukin-15 Is Critical in the Pathogenesis of Influenza A Virus-Induced Acute Lung Injury Reviewed

Risa Nakamura, Naoyoshi Maeda, Kensuke Shibata, Hisakata Yamada, Tetsuo Kase, Yasunobu Yoshikai

Journal of Virology 84 ( 11 ) 5574 - 5582 2010.6

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<title>ABSTRACT</title>

Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of “cytokine storm” has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44
⁺
CD8
⁺
T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8
⁺
T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in β
₂
-microglobulin by gene targeting and those depleted of CD8
⁺
T cells by
<italic>in vivo</italic>
administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8
⁺
T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.

DOI： 10.1128/jvi.02030-09
Antibody-Mediated T-Cell Reduction or Increased Levels of Chimerism Overcome Resistance to Cyclophosphamide-Induced Tolerance in NKT-Deficient Mice Reviewed

T. Onzuka, Y. Tomita, S. Okano, I. Shimizu, H. Yamada, Y. Yoshikai, R. Tominaga

Scandinavian Journal of Immunology 72 ( 2 ) 106 - 117 2010.5

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DOI： 10.1111/j.1365-3083.2010.02417.x
The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury Reviewed

Hirokazu Saiwai, Yasuyuki Ohkawa, Hisakata Yamada, Hiromi Kumamaru, Akihito Harada, Hideyuki Okano, Takehiko Yokomizo, Yukihide Iwamoto, Seiji Okada

The American Journal of Pathology 176 ( 5 ) 2352 - 2366 2010.5

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DOI： 10.2353/ajpath.2010.090839
Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation Reviewed

Kazuhito Gotoh, Yoshihiko Tanaka, Akihiko Nishikimi, Risa Nakamura, Hisakata Yamada, Naoyoshi Maeda, Takahiro Ishikawa, Katsuaki Hoshino, Takehito Uruno, Qinhong Cao, Sadayuki Higashi, Yasushi Kawaguchi, Munechika Enjoji, Ryoichi Takayanagi, Tsuneyasu Kaisho, Yasunobu Yoshikai, Yoshinori Fukui

Journal of Experimental Medicine 207 ( 4 ) 721 - 730 2010.4

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Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity, but also contribute to the pathogenesis of certain autoimmune diseases, by producing large amounts of type I IFNs. Although activation of pDCs is triggered by engagement of nucleotide-sensing toll-like receptors (TLR) 7 and 9, type I IFN induction additionally requires IκB kinase (IKK) α–dependent activation of IFN regulatory factor (IRF) 7. However, the signaling pathway mediating IKK-α activation is poorly defined. We show that DOCK2, an atypical Rac activator, is essential for TLR7- and TLR9-mediated IFN-α induction in pDCs. We found that the exposure of pDCs to nucleic acid ligands induces Rac activation through a TLR-independent and DOCK2-dependent mechanism. Although this Rac activation was dispensable for induction of inflammatory cytokines, phosphorylation of IKK-α and nuclear translocation of IRF-7 were impaired in Dock2-deficient pDCs, resulting in selective loss of IFN-α induction. Similar results were obtained when a dominant-negative Rac mutant was expressed in wild-type pDCs. Thus, the DOCK2–Rac signaling pathway acts in parallel with TLR engagement to control IKK-α activation for type I IFN induction. Owing to its hematopoietic cell-specific expression, DOCK2 may serve as a therapeutic target for type I IFN–related autoimmune diseases.

DOI： 10.1084/jem.20091776
Dual specificity phosphatase16 is a negative regulator of c-Jun NH2-terminal kinase activity in T cells Reviewed

Shino Kumabe, Momoe Itsumi, Hisakata Yamada, Toshiki Yajima, Tetsuya Matsuguchi, Yasunobu Yoshikai

Microbiology and Immunology 54 ( 2 ) 105 - 111 2010.2

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DOI： 10.1111/j.1348-0421.2009.00188.x
Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle Reviewed

Eri Ishikawa, Tetsuaki Ishikawa, Yasu S. Morita, Kenji Toyonaga, Hisakata Yamada, Osamu Takeuchi, Taroh Kinoshita, Shizuo Akira, Yasunobu Yoshikai, Sho Yamasaki

Journal of Experimental Medicine 206 ( 13 ) 2879 - 2888 2009.12

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Tuberculosis remains a fatal disease caused by Mycobacterium tuberculosis, which contains various unique components that affect the host immune system. Trehalose-6,6′-dimycolate (TDM; also called cord factor) is a mycobacterial cell wall glycolipid that is the most studied immunostimulatory component of M. tuberculosis. Despite five decades of research on TDM, its host receptor has not been clearly identified. Here, we demonstrate that macrophage inducible C-type lectin (Mincle) is an essential receptor for TDM. Heat-killed mycobacteria activated Mincle-expressing cells, but the activity was lost upon delipidation of the bacteria; analysis of the lipid extracts identified TDM as a Mincle ligand. TDM activated macrophages to produce inflammatory cytokines and nitric oxide, which are completely suppressed in Mincle-deficient macrophages. In vivo TDM administration induced a robust elevation of inflammatory cytokines in sera and characteristic lung inflammation, such as granuloma formation. However, no TDM-induced lung granuloma was formed in Mincle-deficient mice. Whole mycobacteria were able to activate macrophages even in MyD88-deficient background, but the activation was significantly diminished in Mincle/MyD88 double-deficient macrophages. These results demonstrate that Mincle is an essential receptor for the mycobacterial glycolipid, TDM.

DOI： 10.1084/jem.20091750
Tyrosine Kinase 2 Plays Critical Roles in the Pathogenic CD4 T Cell Responses for the Development of Experimental Autoimmune Encephalomyelitis Reviewed

Akiko Oyamada, Hiori Ikebe, Momoe Itsumi, Hirokazu Saiwai, Seiji Okada, Kazuya Shimoda, Yoichiro Iwakura, Keiichi I. Nakayama, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

The Journal of Immunology 183 ( 11 ) 7539 - 7546 2009.12

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DOI： 10.4049/jimmunol.0902740
Oral administration of xanthan gum enhances antitumor activity through Toll-like receptor 4 Reviewed

Ario Takeuchi, Yoriyuki Kamiryou, Hisakata Yamada, Masatoshi Eto, Kensuke Shibata, Kennichi Haruna, Seiji Naito, Yasunobu Yoshikai

International Immunopharmacology 9 ( 13-14 ) 1562 - 1567 2009.12

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DOI： 10.1016/j.intimp.2009.09.012
Effects of Lipopolysaccharide on the Induction of Mixed Chimerism in Cyclophosphamide-Induced Tolerance Reviewed

T. Onzuka, Y. Tomita, I. Shimizu, S. Okano, H. Yamada, Y. Yoshikai, R. Tominaga

Scandinavian Journal of Immunology 70 ( 5 ) 423 - 430 2009.11

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DOI： 10.1111/j.1365-3083.2009.02314.x
Protective Role of Fas-FasL Signaling in Lethal Infection with Herpes Simplex Virus Type 2 in Mice

Takahiro Ishikawa, Hisakata Yamada, Akiko Oyamada, Fumi Goshima, Yukihiro Nishiyama, Yasunobu Yoshikai

Journal of Virology 83 ( 22 ) 11777 - 11783 2009.11

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<title>ABSTRACT</title>

Herpes simplex virus type 2 (HSV-2) induces acute local infection followed by latent infection in the nervous system and often leads to the development of lethal encephalitis in immunocompromised hosts. The mechanisms of immune protection against lethal HSV-2 infection, however, have not been clarified. In this study, we examined the roles of Fas-Fas ligand (FasL) signaling in lethal infection with HSV-2 by using mice with mutated Fas (
<italic>lpr</italic>
) or FasL (
<italic>gld</italic>
) in C57BL/6 background. Both
<italic>lpr</italic>
and
<italic>gld</italic>
mice exhibited higher mortality than wild-type (WT) C57BL/6 mice after infection with virulent HSV-2 strain 186 and showed significantly increased viral titers in the spinal cord compared with WT mice 9 days after infection, just before the mice started to die. There were no differences in the numbers of CD4
⁺
and CD8
⁺
T cells infiltrated in the spinal cord or in the levels of HSV-2-specific gamma interferon produced by those cells in a comparison of
<italic>lpr</italic>
and WT mice 9 days after infection. Adoptive transfer studies demonstrated that CD4
⁺
T cells from WT mice protected
<italic>gld</italic>
mice from lethal infection by HSV-2. Furthermore, CD4
⁺
T cells infiltrated in the spinal cord of HSV-2-infected WT mice expressed functional FasL that induced apoptosis of Fas-expressing target cells in vitro. These results suggest that FasL-mediated cytotoxic activity of CD4
⁺
T cells plays an important role in host defense against lethal infection with HSV-2.

DOI： 10.1128/jvi.01006-09
IL-15 is critical for the maintenance and innate functions of self-specific CD8+T cells Reviewed

Momoe Itsumi, Yasunobu Yoshikai, Hisakata Yamada

European Journal of Immunology 39 ( 7 ) 1784 - 1793 2009.7

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DOI： 10.1002/eji.200839106
IL-15 protects antigen-specific CD8+T cell contraction afterMycobacterium bovisbacillus Calmette-Guérin infection Reviewed

Ce Tang, Hisakata Yamada, Kensuke Shibata, Shin-ichi Yoshida, Worawidh Wajjwalku, Yasunobu Yoshikai

Journal of Leukocyte Biology 86 ( 1 ) 187 - 194 2009.7

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DOI： 10.1189/jlb.0608363
Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor Reviewed

Yoriyuki Kamiryo, Masatoshi Eto, Hisakata Yamada, Toshiki Yajima, Masahiko Harano, Ario Takeuchi, Katsunori Tatsugami, Masumitsu Hamaguchi, Seiji Naito, Yasunobu Yoshikai

Cancer Research 69 ( 12 ) 5151 - 5158 2009.6

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DOI： 10.1158/0008-5472.can-08-2517
Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity Reviewed

Yukari Shinozaki, Sen Wang, Yoshiyuki Miyazaki, Kohji Miyazaki, Hisakata Yamada, Yasunobu Yoshikai, Hiromitsu Hara, Hiroki Yoshida

International Journal of Cancer 124 ( 6 ) 1372 - 1378 2009.3

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DOI： 10.1002/ijc.24107
A Novel Role of CD30L/CD30 Signaling by T-T Cell Interaction in Th1 Response against Mycobacterial Infection Reviewed

Ce Tang, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Worawidh Wajjwalku, Eckhard R. Podack, Yasunobu Yoshikai

The Journal of Immunology 181 ( 9 ) 6316 - 6327 2008.11

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DOI： 10.4049/jimmunol.181.9.6316
Role of the Cytokine Profiles Produced by Invariant Natural Killer T Cells in the Initial Phase of Cyclophosphamide-Induced Tolerance Reviewed

Tatsushi Onzuka, Yukihiro Tomita, Ichiro Shimizu, Shinji Okano, Hisakata Yamada, Yasunobu Yoshikai, Ryuji Tominaga

Transplantation 86 ( 9 ) 1301 - 1310 2008.11

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DOI： 10.1097/tp.0b013e318187265e
Identification of CD25+ γδ T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers Reviewed

Kensuke Shibata, Hisakata Yamada, Risa Nakamura, Xun Sun, Momoe Itsumi, Yasunobu Yoshikai

The Journal of Immunology 181 ( 9 ) 5940 - 5947 2008.11

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DOI： 10.4049/jimmunol.181.9.5940
The Cytokine RANKL Produced by Positively Selected Thymocytes Fosters Medullary Thymic Epithelial Cells that Express Autoimmune Regulator Reviewed

Yu Hikosaka, Takeshi Nitta, Izumi Ohigashi, Kouta Yano, Naozumi Ishimaru, Yoshio Hayashi, Mitsuru Matsumoto, Koichi Matsuo, Josef M. Penninger, Hiroshi Takayanagi, Yoshifumi Yokota, Hisakata Yamada, Yasunobu Yoshikai, Jun-ichiro Inoue, Taishin Akiyama, Yousuke Takahama

Immunity 29 ( 3 ) 438 - 450 2008.9

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DOI： 10.1016/j.immuni.2008.06.018
Tyk2-Signaling Plays an Important Role in Host Defense against Escherichia coli through IL-23-Induced IL-17 Production by γδ T Cells Reviewed

Risa Nakamura, Kensuke Shibata, Hisakata Yamada, Kazuya Shimoda, Keiichi Nakayama, Yasunobu Yoshikai

The Journal of Immunology 181 ( 3 ) 2071 - 2075 2008.8

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DOI： 10.4049/jimmunol.181.3.2071
Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis Reviewed

N Kaibara, H Yamada, T Shuto, Y Nakashima, K Okazaki, H Miyahara, Y Esaki, G Hirata, Y Iwamoto

Histopathology 52 ( 7 ) 856 - 864 2008.6

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DOI： 10.1111/j.1365-2559.2008.03050.x
Efficacy of Recombinant Bacille Calmette‐Guérin Vaccine Secreting Interleukin‐15/Antigen 85B Fusion Protein in Providing Protection againstMycobacterium tuberculosis Reviewed

Ce Tang, Hisakata Yamada, Kensuke Shibata, Naoyoshi Maeda, Shinichi Yoshida, Worawidh Wajjwalku, Naoya Ohara, Takeshi Yamada, Taroh Kinoshita, Yasunobu Yoshikai

The Journal of Infectious Diseases 197 ( 9 ) 1263 - 1274 2008.5

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DOI： 10.1086/586902
A Critical Role of CD30 Ligand/CD30 in Controlling Inflammatory Bowel Diseases in Mice Reviewed

Xun Sun, Shinichi Somada, Kensuke Shibata, Hiromi Muta, Hisakata Yamada, Hirofumi Yoshihara, Kuniomi Honda, Kazuhiko Nakamura, Ryhoichi Takayanagi, Kenzaburo Tani, Eckhard R. Podack, Yasunobu Yoshikai

Gastroenterology 134 ( 2 ) 447 - 458.e3 2008.2

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DOI： 10.1053/j.gastro.2007.11.004
A regulatory role of interleukin 15 in wound healing and mucosal infection in mice Reviewed

Yoshiko Kagimoto, Hisakata Yamada, Takahiro Ishikawa, Naoyoshi Maeda, Fumi Goshima, Yukihiro Nishiyama, Masutaka Furue, Yasunobu Yoshikai

Journal of Leukocyte Biology 83 ( 1 ) 165 - 172 2008.1

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DOI： 10.1189/jlb.0307137
Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis Reviewed

H Yamada, Y Nakashima, K Okazaki, T Mawatari, J-I Fukushi, N Kaibara, A Hori, Y Iwamoto, Y Yoshikai

Annals of the Rheumatic Diseases 67 ( 9 ) 1299 - 1304 2007.11

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DOI： 10.1136/ard.2007.080341
IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17 Reviewed

Kazufumi Yoshihara, Hisakata Yamada, Akiko Hori, Toshiki Yajima, Chiharu Kubo, Yasunobu Yoshikai

European Journal of Immunology 37 ( 10 ) 2744 - 2752 2007.10

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DOI： 10.1002/eji.200737229
Interleukin-15 selectively expands CD57+CD28−CD4+ T cells, which are increased in active rheumatoid arthritis Reviewed

Hisakata Yamada, Nobutaka Kaibara, Shinji Okano, Takeshi Maeda, Toshihide Shuto, Yasuharu Nakashima, Ken Okazaki, Yukihide Iwamoto

Clinical Immunology 124 ( 3 ) 328 - 335 2007.9

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DOI： 10.1016/j.clim.2007.06.001
In vivo treatment with a nonapeptide thymic hormone, facteur thymique serique (FTS), ameliorates chronic colitis induced by dextran sulphate sodium in mice Reviewed

Xun Sun, Hisakata Yamada, Kazufumi Yoshihara, Akira Awaya, Yasunobu Yoshikai

International Immunopharmacology 7 ( 7 ) 928 - 936 2007.7

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DOI： 10.1016/j.intimp.2007.02.014
Resident Vδ1+γδ T Cells Control Early Infiltration of Neutrophils afterEscherichia coliInfection via IL-17 Production Reviewed

Kensuke Shibata, Hisakata Yamada, Hiromitsu Hara, Kenji Kishihara, Yasunobu Yoshikai

The Journal of Immunology 178 ( 7 ) 4466 - 4472 2007.4

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DOI： 10.4049/jimmunol.178.7.4466
Tyk2 Signaling in Host Environment Plays an Important Role in Contraction of Antigen-Specific CD8+T Cells following a Microbial Infection Reviewed

Wei Li, Hisakata Yamada, Toshiki Yajima, Ryusuke Nakagawa, Kazuya Shimoda, Keiichi Nakayama, Yasunobu Yoshikai

The Journal of Immunology 178 ( 7 ) 4482 - 4488 2007.4

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DOI： 10.4049/jimmunol.178.7.4482
H2-M3-Restricted CD8+T Cells Induced by Peptide-Pulsed Dendritic Cells Confer Protection againstMycobacterium tuberculosis Reviewed

Takehiko Doi, Hisakata Yamada, Toshiki Yajima, Worawidh Wajjwalku, Toshiro Hara, Yasunobu Yoshikai

The Journal of Immunology 178 ( 6 ) 3806 - 3813 2007.3

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DOI： 10.4049/jimmunol.178.6.3806
Lipopolysaccharide inhalation exacerbates allergic airway inflammation by activating mast cells and promoting Th2 responses Reviewed

D. Murakami, H. Yamada, T. Yajima, A. Masuda, S. Komune, Y. Yoshikai

Clinical & Experimental Allergy 37 ( 3 ) 339 - 347 2007.3

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DOI： 10.1111/j.1365-2222.2006.02633.x
Enforced Expression of Bcl-2 Partially Restores Cell Numbers but Not Functions of TCRγδ Intestinal Intraepithelial T Lymphocytes in IL-15-Deficient Mice Reviewed

Kenji Nakazato, Hisakata Yamada, Toshiki Yajima, Yoshiko Kagimoto, Hiroyuki Kuwano, Yasunobu Yoshikai

The Journal of Immunology 178 ( 2 ) 757 - 764 2007.1

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DOI： 10.4049/jimmunol.178.2.757
IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells Reviewed

N AOI, T MASUDA, D MURAKAMI, T YAJIMA, H MIZUBUCHI, H YAMADA, H KAWAUCHI, Y YOSHIKAI

Journal of Allergy and Clinical Immunology 117 ( 6 ) 1359 - 1366 2006.6

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DOI： 10.1016/j.jaci.2006.02.018
Impaired Protection againstMycobacterium bovisBacillus Calmette-Guérin Infection in IL-15-Deficient Mice Reviewed

Kimika Saito, Toshiki Yajima, Shino Kumabe, Takehiko Doi, Hisakata Yamada, Subash Sad, Hao Shen, Yasunobu Yoshikai

The Journal of Immunology 176 ( 4 ) 2496 - 2504 2006.2

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DOI： 10.4049/jimmunol.176.4.2496
Pristane, a Non-Antigenic Adjuvant, Induces MHC Class II-Restricted, Arthritogenic T Cells in the Rat Reviewed

Jens Holmberg, Jonatan Tuncel, Hisakata Yamada, Shemin Lu, Peter Olofsson, Rikard Holmdahl

The Journal of Immunology 176 ( 2 ) 1172 - 1179 2006.1

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DOI： 10.4049/jimmunol.176.2.1172
The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans Reviewed

Balik Dzhambazov, Meirav Holmdahl, Hisakata Yamada, Shemin Lu, Mikael Vestberg, Bj�rn Holm, Olof Johnell, Jan Kihlberg, Rikard Holmdahl

European Journal of Immunology 35 ( 2 ) 357 - 366 2005.2

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DOI： 10.1002/eji.200425637
A Transient Post-Translationally Modified Form of Cartilage Type II Collagen Is Ignored by Self-Reactive T Cells Reviewed

Hisakata Yamada, Balik Dzhambazov, Robert Bockermann, Thomas Blom, Rikard Holmdahl

The Journal of Immunology 173 ( 7 ) 4729 - 4735 2004.10

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DOI： 10.4049/jimmunol.173.7.4729
The Critical Role of Fas-Fas Ligand Interaction in Donor-Specific Transfusion-Induced Tolerance to H-Y Antigen Reviewed

Ryosuke Minagawa, Shinji Okano, Yukihiro Tomita, Kenji Kishihara, Hisakata Yamada, Kenichi Nomoto, Mitsuo Shimada, Yoshihiko Maehara, Keizo Sugimachi, Yasunobu Yoshikai, Kikuo Nomoto

Transplantation 78 ( 6 ) 799 - 806 2004.9

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DOI： 10.1097/01.tp.0000129799.96439.6f
Mechanism of murine Vγ1+ γ δ T cell-mediated innate immune response againstListeria monocytogenes infection Reviewed

Goro Matsuzaki, Hisakata Yamada, Kenji Kishihara, Yasunobu Yoshikai, Kikuo Nomoto

European Journal of Immunology 32 ( 4 ) 928 - 935 2002.4

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DOI： 10.1002/1521-4141(200204)32:4<928::aid-immu928>3.0.co;2-i
Involvement of CD4+,CD57+ T cells in the disease activity of rheumatoid arthritis Reviewed

Takeshi Maeda, Hisakata Yamada, Ryuji Nagamine, Toshihide Shuto, Yasuharu Nakashima, Go Hirata, Yukihide Iwamoto

Arthritis & Rheumatism 46 ( 2 ) 379 - 384 2002.2

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DOI： 10.1002/art.10133
The molecular pathogenesis of collagen-induced arthritis in mice—a model for rheumatoid arthritis Reviewed

R HOLMDAHL, R BOCKERMANN, J BACKLUND, H YAMADA

Ageing Research Reviews 1 ( 1 ) 135 - 147 2002.2

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DOI： 10.1016/s0047-6374(01)00371-2
Evidence of the extrathymic development of tyrosinase-related protein-2-recognizing CD8+ T cells with low avidity Reviewed

Mamoru Harada,, Hisakata Yamada, Katsunori Tatsugami, Kikuo Nomoto

Immunology 104 ( 1 ) 67 - 74 2001.9

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DOI： 10.1046/j.1365-2567.2001.01278.x
Reevaluation of the origin of CD44high "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells Reviewed

Hisakata Yamada, Goro Matsuzaki, QiJie Chen, Yukihide Iwamoto, Kikuo Nomoto

European Journal of Immunology 31 ( 6 ) 1917 - 1926 2001.6

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DOI： 10.1002/1521-4141(200106)31:6<1917::aid-immu1917>3.0.co;2-f
CYCLOPHOSPHAMIDE-INDUCED TOLERANCE IN RAT ORTHOTOPIC LIVER TRANSPLANTATION1 Reviewed

Shinji Okano, Masatoshi Eto, Yukihiro Tomita, Tomoharu Yoshizumi, Hisakata Yamada, Ryosuke Minagawa, Kenichi Nomoto, Keizo Sugimachi, Kikuo Nomoto

Transplantation 71 ( 3 ) 447 - 456 2001.2

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DOI： 10.1097/00007890-200102150-00019
Persistent infection with Listeria monocytogenes in the kidney induces anti-inflammatory invariant fetal-type γδ T cells Reviewed

H. Ikebe, H. Yamada, M. Nomoto, H. Takimoto, T. Nakamura, K.-H. Sonoda, K. Nomoto

Immunology 102 ( 1 ) 94 - 102 2001.1

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DOI： 10.1046/j.1365-2567.2001.01149.x
Successful Priming and Tolerization of T Cells to Orally Administered Antigens in B-Cell-Deficient Mice Reviewed

Asako Hashimoto, Hisakata Yamada, Goro Matsuzaki, Kikuo Nomoto

Cellular Immunology 207 ( 1 ) 36 - 40 2001.1

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DOI： 10.1006/cimm.2000.1738
Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8+ T cells Reviewed

Hisakata Yamada, Goro Matsuzaki, Yukihide Iwamoto, Kikuo Nomoto

International Immunology 12 ( 12 ) 1677 - 1683 2000.12

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DOI： 10.1093/intimm/12.12.1677
TCR-Independent Activation of Extrathymically Developed, Self Antigen-Specific T Cells by IL-2/IL-15 Reviewed

Hisakata Yamada, Takahiko Nakamura, Goro Matsuzaki, Yukihide Iwamoto, Kikuo Nomoto

The Journal of Immunology 164 ( 4 ) 1746 - 1752 2000.2

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DOI： 10.4049/jimmunol.164.4.1746
Positive Selection of Extrathymically Developed T Cells by Self-antigens Reviewed

Hisakata Yamada, Toshiharu Ninomiya, Asako Hashimoto, Koji Tamada, Hiroaki Takimoto, Kikuo Nomoto

Journal of Experimental Medicine 188 ( 4 ) 779 - 784 1998.8

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Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen–specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen–specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen–specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor β chain (IL-2Rβ) and intermediate levels of CD3 (CD3int) but were natural killer cell (NK)1.1−. They rapidly produced interferon γ but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3intIL-2Rβ+NK1.1− cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3intIL-2Rβ+NK1.1− cells in normal mice are also positively selected by self-antigens.

DOI： 10.1084/jem.188.4.779
Macrophages activated by Listeria monocytogenes induce organ‐specific autoimmunity Reviewed

K.‐H. SONODA, G. MATSUZAKI, A. NOMURA, H. YAMADA, S. HAMANO, T. NAKAMURA, A. MUKASA, K. NOMOTO

Immunology 92 ( 2 ) 274 - 283 1997.10

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DOI： 10.1046/j.1365-2567.1997.00342.x
p56lckis not essential for the T-cell response to allo-MHC antigens Reviewed

H. YAMADA, Y.-Y. KONG, K. KISHIHARA, T. W. MAK, K. NOMOTO

Immunology 92 ( 1 ) 33 - 38 1997.9

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DOI： 10.1046/j.1365-2567.1997.d01-2297.x
The characterization of testicular cell (TC)‐specific T‐cell clones induced by intratesticular Listeria monocytogenes infection: TC‐specific T cells with atypical cytokine profile transfer orchitis Reviewed

G. MATSUZAKI, K.‐H. SONODA, A. MUKASA, H. YAMADA, T. NAKAMURA, H. IKEBE, S. HAMANO, K. NOMOTO

Immunology 91 ( 4 ) 520 - 528 1997.8

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DOI： 10.1046/j.1365-2567.1997.00306.x
Enhanced generation of NK cells with intact cytotoxic function in CD45 exon 6-deficient mice Reviewed

Yamada H, Kishihara K, Kong YY, Nomoto K

J Immunol 157 ( 4 ) 1523 - 1528 1996.8

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Books

レビンソン微生物学・免疫学

山田久方（Role：Joint translator）

2012.10

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Language：Japanese Book type：Scholarly book
疾患モデルの作製と利用－免疫疾患

山田久方（Role：Joint author）

2011.6

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Language：Japanese Book type：Scholarly book
エッセンシャル免疫学　第２版

平野俊夫、村上正晃、鍔田武志、福井宣規、阪口篤雄、松井健、鈴木春己、湊長博、濱崎洋子、烏山一、審良静男、加藤博己、菅村和夫、小池隆夫、橋本陶子、吉開泰信、山田久方、清野宏、吉田理人

2010.8

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Book type：General book, introductory book for general audience
エッセンシャル免疫学

平野俊夫、村上正晃、鍔田武志、福井宣規、阪口篤雄、松井健、鈴木春己、湊長博、濱崎洋子、烏山一、審良静男、加藤博己、菅村和夫、小池隆夫、橋本陶子、吉開泰信、山田久方、清野宏、吉田理人

2007.3

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Book type：Scholarly book

Presentations

ヒト関節リウマチとTh17細胞 Invited

山田久方

第37回日本臨床免疫学会総会 2009.11

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Event date： 2009.11

Presentation type：Symposium, workshop panel (public)

Country：Japan
関節リウマチ滑膜組織培養法の開発

櫻庭康司, 藤村謙次郎, 宮原寿明, 江崎幸雄, 岩本幸英, 吉開泰信, 山田久方

第42回日本臨床免疫学会総会 2014.9

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Event date： 2014.9

Language：Japanese

Venue：東京都 Country：Japan
自己II型コラーゲンの転写後修飾が自己免疫寛容に及ぼす影響

山田久方, Johan Backlund, 小山田亜希子, Rikard Holmdahl, 吉開泰信

第41回日本臨床免疫学会総会 2013.11

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Event date： 2013.11

Language：Japanese

Venue：下関市 Country：Japan
異なるTh1細胞サブセットの分化、機能におけるTyk2の役割

橋口智光, 小山田亜希子, 櫻庭康司, 吉開泰信, 山田久方

第24回日本生体防御学会学術総会 2013.7

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Event date： 2013.7

Language：Japanese Presentation type：Oral presentation (general)

Venue：熊本市 Country：Japan
アダリムマブはBio-naiveでMTX併用の関節リウマチにおいて寛解導入・維持に有用である

田代泰隆、中島康晴、岡崎賢、馬渡太郎、福士純一、糸川高史、大石正信、山田久方、岩本幸英

第56回日本リウマチ学会総会・学術集会 2012.4

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Event date： 2012.4

Country：Japan
抗原特異的Th17細胞のクローン増殖におけるIL-2の役割

藤村謙次郎、橋口智光、櫻庭康司、小山田亜希子、岩本幸英、吉開泰信、山田久方

第56回日本リウマチ学会総会・学術集会 2012.4

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Event date： 2012.4

Country：Japan
内科と整形外科とのチーム医療　整形外科の立場から

中島康晴、山田久方、岡崎賢、馬渡太郎、福士純一、糸川高史、大石正信、田代泰隆、岩本幸英

第56回日本リウマチ学会総会・学術集会 2012.4

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Event date： 2012.4

Country：Japan
関節リウマチにおけるBio-naiveおよびswitch症例でのアダリムマブ使用成績

田代泰隆、中島康晴、岡崎賢、馬渡太郎、福士純一、糸川高史、大石正信、山田久方、橋爪誠、岩本幸英

第43回九州リウマチ学会 2012.3

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Event date： 2012.3

Country：Japan
生物製剤投与中にTHAの遅発性感染が発生したRAの１例

福徳款章、中島康晴、大石正信、岡崎賢、馬渡太郎、福士純一、糸川高史、田代泰隆、山田久方、岩本幸英

第43回九州リウマチ学会 2012.3

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Event date： 2012.3

Country：Japan
関節リウマチの最新の病因論 Invited

山田久方

Effort Consortium 2012 2012.3

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Event date： 2012.3

Presentation type：Oral presentation (invited, special)

Venue：名古屋 Country：Japan
Differential requirement for IL-2-signaling in clonal expansion of Th1 and Th17 cells in vivo

FujimuraKenjiro, Oyamada Akiko, Yoshikai Yasunobu, Yamada Hisakata

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
The critical role of CD30L in early protection against Listeria monocytogenes in innate γδ T cells in mice

Guo Ying, Sun Xun, Shibata Kensuke, Huang Yinxia, Yamada Hisakata, Muta Hiromi, Eckhard R. Podack, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
Regulatory CD8 T cells expressing CD122 and programmed death-1 are distinct subset of memory phenotype CD8 T cells

Sakuraba Koji, Fujimura Kenjiro, Oyamada Akiko, Yoshikai Yasunobu, Yamada Hisakata

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
The critical role of CD30L in maintenance and activation of naturally occurring IL-17A-producing gammadelta T cells in mice.

Sun Xun, Guo Ying, Shibata Kensuke, Huang Yinxia, Yamada Hisakata, Muta Hiromi, Eckhard R. Podack, Yoshikai Yasunobu,

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
The role of Tyk2 in maintenance and activation of naturally occurring IL-17A-producing γδ T cells in mice.

Oyamada Akiko, Shibata Kensuke, Yoshikai Yasunobu, Yamada Hisakata

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
A protective role of naturally occurring IL-17A-producing γδ T cells in the lung at the early stage of systemic candidiasis in mice

Dejima Takashi, Shibata Kensuke, Yamada Hisakata, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
IL-7-receptor-α-mediated signaling is required for the development of naturally occurring IL-17-producing γδ T cells in the adult thymus

Nakamura Masataka, Shibata Kensuke, Yamada Hisakata, Ikuta Koichi, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
Naturally occurring IL-17-producing γδ T cells commit at the DN2 stage of mouse fetal thymus in Notch-dependent manner.

Shibata Kensuke, Yamada Hisakata, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
Type I interferon limits acute lung injury caused by influenza A H1N1 virus via down-modulation of excessive immune responses in mice.

ARIMORI Yojiro, Nakamura Risa, Maeda Naoyoshi, Shibata Kensuke, Yamada Hisakata, Kase Tetsuo, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
The possibility of the treatment targeting Interleukin-15 or CD8 T cells against the pathogenesis of influenza A virus–induced acute lung injury.

Nakamura Risa, Maeda Naoyoshi, Shibata Kensuke, Yamada Hisakata, Ohteki Toshiaki, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
Hematopoietic cell-induced positive selection of self antigen-specific CD8 T cells.

Yamada Hisakata, Yoshikai Yasunobu

第40回日本免疫学会総会・学術集会 2011.11

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Event date： 2011.11

Country：Japan
抗原特異的Th17細胞増殖におけるIL-2レセプターaの役割

藤村謙次郎、小山田亜希子、岩本幸英、吉開泰信、山田久方

第55回日本リウマチ学会総会・学術集会 2011.7

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Event date： 2011.7

Country：Japan
関節リウマチにおける脊椎強度評価 -骨皮質シェルと海面骨の加重分担-

馬渡太郎、中島康晴、山田久方、岡崎賢、福士純一、糸川高史、大石正信、田代泰隆、T.M. Keaveny、岩本幸英

第55回日本リウマチ学会総会・学術集会 2011.7

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Event date： 2011.7

Country：Japan
マイコバクテリア感染に関与するT細胞応答におけるTyrosine kinase 2 (Tyk2)の重要性

小山田亜希子、吉開泰信、山田久方

第22回日本生体防御学会学術総会 2011.7

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Event date： 2011.6 - 2011.7

Country：Japan
Notch-Hes1経路は自然発生IL-17産生γδT細胞分化に必要である

柴田健輔、山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
IL-17による自然発生IL-17産生γδT細胞機能制御機構の解析

中村真隆、柴田健輔、山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
自然発生IL-17産生γδT細胞活性化におけるCD30Ligandの役割

孫遜、郭颖、黄銀霞、柴田健輔、山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
Candida albicans感染防御におけるIL-17産生γδT細胞の役割

出嶋卓、柴田健輔、山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
致死性インフルエンザ感染におけるⅠ型インターフェロンの役割

有森陽二郎、中村梨沙、柴田健輔、山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
インターロイキン‐15を標的にしたインフルエンザAウイルス感染による急性肺障害の治療の開発研究

中村梨沙、前田直良、柴田健輔、山田久方、加瀬哲男、樗木俊聡、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
ヒト関節リウマチにおけるCD4T細胞サブセットの検討

山田久方、吉開泰信

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
抗原特異的Th17細胞のクローン増殖におけるIL-2の役割

藤村謙次郎、櫻庭康司、小山田亜希子、吉開泰信、山田久方

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
免疫制御作用を持つメモリー型PD-1陽性CD8T細胞の特徴

櫻庭康司、小山田亜希子、藤村謙次郎、吉開泰信、山田久方

第22回日本生体防御学会学術総会 2011.6

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Event date： 2011.6 - 2011.7

Country：Japan
Critical role of DOCK2 in type I IFN induction in plasmacytoid dendriic cells

K. Gotoh, Y. Tanaka, A. Nishikimi, R. Nakamura, H. Yamada, K. Hoshino, T. Kaisho, Y. Yoshikai, Y. Fukui

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
CD30 ligand/CD30 play a critical role in Th17 differentiation in mice

X. Sun, H. Yamada, K. Shibata, H. Muta, K. Tani, E. Podack, Y. Yoshikai

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
The basic helix-loop-helix protein HES1 controls the differentiation of naturally occurring interleukin (IL)-17-producing γδ T cells

K. Shibata, H. Yamada, T. Sato, H. Hara, S. Yamasaki, R. Kageyama, Y. Yoshikai

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
A protective role of IL-17-producing γδ T cells in lung against systemic candidasis

T. Dejima, K. SHibata, H. Yamada, Y. Yoshikai

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
Tyk2 is indespensable ofr the development of experimental autoimmune disease

A. Oyamada, Y. Yoshikai, H. Yamada

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
Preferential accumulation of Th1 cells in the joints of rheumatoid arthritis and osteoarthritis

H. Yamada, A. Oyamada, Y. Yoshikai

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
Interleukin-15 is critical in the pathogenesis of influenza A virus-induced acute lung injury

R. Nakamura, N. Maeda, O. Noyori, K. Shibata, H. Yamada, Y. Yoshikai

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury

H. Saiwai, Y. Ohkawa, H. Yamada, H. Kumamaru, A. Harada, T. Yokomizo, Y. Iwamoto, S. Okada

第14回国際免疫学会 (14th International Congress of Immunology) 2010.8

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Event date： 2010.8

Country：Japan
マウスコラーゲン誘導性関節炎におけるTyk2の重要性

小山田亜希子、吉開泰信、山田久方

第21回日本生体防御学会学術総会 2010.7

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Event date： 2010.7

Country：Japan
The basic helix-loop-helix protein HES1は自然発生IL-17産生γδT細胞分化に必要である

柴田健輔、山田久方、吉開泰信

第21回日本生体防御学会学術総会 2010.7

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Event date： 2010.7

Country：Japan
インターロイキン-15はインフルエンザAウイルス感染による急性肺障害の病態形成に重要である

中村梨紗、前田直良、柴田健輔、山田久方、加瀬哲男、吉開泰信

第21回日本生体防御学会学術総会 2010.7

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Event date： 2010.7

Country：Japan
関節リウマチ患者における脂質異常

秋山美緒、馬渡太郎、福士純一、岡崎賢、中島康晴、山田久方、小山田亜希子、岩本幸英

第83回日本整形外科学会学術集会 2010.5

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Event date： 2010.5

Country：Japan
関節リウマチ患者における脂質異常

秋山美緒、馬渡太郎、中島康晴、岡崎賢、福士純一、山田久方、小山田亜希子、岩本幸英

第54回日本リウマチ学会総会・学術集会 2010.4

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Event date： 2010.4

Country：Japan
マウスコラーゲン誘導性関節炎におけるTyk2の重要性

小山田亜希子、藤村謙次郎、岩本幸英、吉開泰信、山田久方

第54回日本リウマチ学会総会・学術集会 2010.4

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Event date： 2010.4

Country：Japan
インフリキシマブによる関節破壊抑制効果の検討

中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、田代泰隆、都留智巳、岩本幸英

第54回日本リウマチ学会総会・学術集会 2010.4

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Event date： 2010.4

Country：Japan
関節破壊と生物学的製剤の効果　-小関節と加重関節の違い-

中島康晴、岡崎賢、馬渡太郎、福士純一、田代泰隆、秋山美緒、山田久方、都留智巳、岩本幸英

第54回日本リウマチ学会総会・学術集会 2010.4

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Event date： 2010.4

Country：Japan
ステロイド性膝骨壊死に伴う関節破壊に対する鏡視下治療の経験

田代泰隆、三浦裕正、中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、橋爪誠、岩本幸英

第39回九州リウマチ学会 2010.3

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Event date： 2010.3

Country：Japan
関節リウマチ患者における脂質異常

秋山美緒、馬渡太郎、福士純一、中島康晴、岡崎賢、山田久方、小山田亜希子、岩本幸英

第39回九州リウマチ学会 2010.3

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Event date： 2010.3

Country：Japan
IL-15は自己抗原特異的CD8陽性T細胞の維持と自然免疫機能に重要である

山田久方、逸見百江、吉開泰信

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
高病原性インフルエンザウイルス(H1N1)感染で誘導される致死的肺傷害病態の解析

中村梨紗、前田直良、野依修、山田久方、柴田健輔、吉開泰信

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
BCG膀胱内注入療法の抗腫瘍効果にはgdT細胞によるIL-17産生が重要である

武内在雄、山田久方、柴田健輔、吉開泰信

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
CD30 ligand play an important role in development of chronic colitis by modulating T-helper 17 differentiation

Xun Sun, Hisakata Yamada, Kensuke SHibata, Hiromi Muta, Kenzaburo Tani, Eckhard R Podack, Yoichiro Iwakura, Yasunobu Yoshikai

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
Tyk2 is indispensable for the development of experimental autoimmune encephalomyelitis and collagen induced arthritis

小山田亜希子、池辺日王里、逸見百江、吉開泰信、山田久方

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
A protective role of IL-17-producing gd T cells in lung against systemic candidasis

出島卓、柴田健輔、山田久方、吉開泰信

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
胸腺におけるIL-17産生γδT細胞転写制御機構の解析

柴田健輔、山田久方、吉開泰信

第39回日本免疫学会総会・学術集会 2009.12

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Event date： 2009.12

Country：Japan
IL-15は自己抗原特異的CD8T細胞の維持や機能を制御する

逸見百江、吉開泰信、山田久方

第20回日本生体防御学会学術総会 2009.7

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Event date： 2009.7

Venue：東京都 Country：Japan
Th17細胞分化におけるCD30リガンドの役割

孫遜、山田久方、柴田健輔、牟田浩実、谷憲三朗、Eckhard R. Podack、岩倉洋一郎、吉開泰信

第20回日本生体防御学会学術総会 2009.7

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Event date： 2009.7

Venue：東京都 Country：Japan
IL-17産生γδT細胞分化に関わる転写制御機構の解析

柴田健輔、山田久方、吉開泰信

第20回日本生体防御学会学術総会 2009.7

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Event date： 2009.7

Venue：東京都 Country：Japan
マウス実験性腸炎モデルを用いてのCD30リガンド／CD３０の炎症性腸疾患における役割の解明

孫　遜、山田久方、柴田健輔、牟田浩実、谷憲三朗、Eckhard R. Podack、吉開泰信

第１９回日本生体防御学会学術総会 2008.7

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Event date： 2009.7 - 2008.7

Country：Japan
関節リウマチの関節内CD4T細胞サブセットの解析

山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、小山田亜希子、岩本幸英

第53回日本リウマチ学会総会・学術集会 2009.4

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Event date： 2009.4

Venue：東京都 Country：Japan
転写因子C/EBPβは関節炎での様々な炎症誘因反応を調節する多機能因子である

岡崎賢、林田光正、中島康晴、馬渡太郎、福士純一、山田久方、岩本幸英

第53回日本リウマチ学会総会・学術集会 2009.4

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Event date： 2009.4

Country：Japan
マウスモデル自己免疫疾患発症におけるTyk2の重要性

小山田亜希子、岩本幸英、山田久方

第53回日本リウマチ学会総会・学術集会 2009.4

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Event date： 2009.4

Venue：東京都 Country：Japan
骨髄由来細胞による自己抗原特異的CD8T細胞の選択的分化

山田久方、逸見百江、吉開泰信

第２８回日本胸腺研究会 2009.2

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Event date： 2009.2

Country：Japan
CD25陽性IL-17産生γδT細胞は胎児胸線で機能分化を果たす

柴田健輔,　山田久方,　中村梨沙,　孫遜,　逸見百江,　吉開泰信

第２８回日本胸腺研究会 2009.2

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Event date： 2009.2

Country：Japan
A critical role of IL-15 in acute lung injury induced by influenza virus infection in mice

MAEDA Naoyoshi, TANG Ce, SHIBATA Kensuke, ITSUMI Momoe, YAMADA Hisakata, KASE Tetsuo, YOSHIKAI Yasunobu

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Cyclophosphamide contributes to the antitumor effects of nonmyeloablative allogeneic stem cell transplantation via a reduction of CD4+CD25+Foxp3+ regulatory T cells.

Ario Takeuchi HisakataYamada Masatoshi Etoh, Yoriyuki Kamiryo, Seiji Naito and Yasunobu Yoshika

第３８回日本免疫学会総会・学術総会 2009.12

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Event date： 2008.12

Country：Japan
CD30L/CD30 signaling by T-T cell interaction augments Th1 responses

Ce Tang, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Wajjiwaalku Worawidh, Eckhard R. Podack and Yasunobu Yoshikai

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Positive selection of self antigen-specific memory-phenotype CD8 T cells by hematopietic cells

YAMADA Hisakata, ITSUMI Momoe, and YOSHIKAI Yasunobu

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
IL-15 regulates development and functions of self antigen-specific memory-phenotype CD8 T cells

ITSUMI Momoe, YOSHIKAI Yasunobu, YAMADA Hisakata

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Tyk2 is indispensable for the development of experimental autoimmune encephalomyelitis

OYAMADA Akiko, IKEBE Hiori, ITSUMI Momoe, YOSHIKAI Yasunobu, YAMADA Hisakata

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Vaccination with dendritic cells overexpressing IL-15 efficiently induced CD8 T cell responses in the absence of CD4 cells

TERADA Maiko, YAMADA Hisakata, OYAMADA Akiko, YOSHIKAI Yasunobu

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Tyk2-signaling plays an important role in host defense against Escherichia coli through IL-23-induced IL-17 production by γδ T cells.

NAKAMURA Risa, SHIBATA Kensuke, YAMADA Hisakata, SHIMODA Kazuya, YOSHIKAI Yasunobu

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
Identification of CD25+γδT cells as fetal thymus-derived naturally occurring IL-17 producers.

Kensuke Shibata, Hisakata Yamada, Risa Nakamura, Xun Sun, Momoe Itsumi, Yasunobu Yoshikai

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
A critical role of CD30 ligand in colitis induced by dextran sulphate sodium in mice

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard R. Podack, and Yasunobu Yoshikai

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
A protective role of Fas/FasL-mediated signaling in lethal infection with herpes simplex virus type 2 infection in mice

Takahiro Ishikawa, Hisakata Yamada, Naoyoshi Maeda, Yukihiro Nishiyama, Yasunobu Yoshikai

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
A protective role of Fas/FasL-mediated signaling in lethal infection with herpes simplex virus type 2 infection in mice

Takahiro Ishikawa, Hisakata Yamada, Naoyoshi Maeda, Yukihiro Nishiyama, Yasunobu Yoshikai

第３８回日本免疫学会総会・学術総会 2008.12

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Event date： 2008.12

Country：Japan
関節リウマチの関節内CD4T細胞の解析

山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、堀亜希子、岩本幸英

第２３回日本整形外科学会基礎学術総会 2009.10

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Event date： 2008.10

Country：Japan
ヒト関節リウマチにおけるTh17 Invited

山田久方

第３６回日本臨床免疫学会総会 2008.10

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Event date： 2008.10

Presentation type：Symposium, workshop panel (public)

Country：Japan
生物学的製剤使用中のリウマチ患者における整形外科手術の検討

福士純一、中島康晴、岡崎賢、馬渡太郎、岩本幸英、山田久方、小山田亜希子、首藤敏秀、都留智巳

第３６回九州リウマチ学会 2008.9

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Event date： 2008.9

Country：Japan
実験的自己免疫性脳脊髄炎におけるTyk2の役割

小山田亜希子、池辺日王里、中山敬一、吉開泰信、山田久方

第１９回日本生体防御学会学術総会 2008.7

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Event date： 2008.7

Country：Japan
IL-17産生γδT細胞はCD25陽性CD122陰性で、胎児胸線で機能分化を果たす

柴田健輔、山田久方　中村梨沙　孫遜　逸見百恵　吉開泰信

第１９回日本生体防御学会学術総会 2008.7

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Event date： 2008.7

Country：Japan
RAにおける関節予後の検討　ーインフリキシマブとMTX使用例の比較ー

中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、堀亜希子、吉澤誠司、都留智巳、首藤敏秀、岩本幸英

第５２回日本リウマチ学会 2008.4

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Event date： 2008.4

Country：Japan
関節リウマチにおけるIL-17産生T細胞の解析

山田久方、貝原信孝、堀亜希子、中島康晴、岡崎賢、馬渡太郎、福士純一、岩本幸英

第51回日本リウマチ学会総会・学術集会 2007.4

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Venue：横浜市　平成19年4月26-29日 Country：Japan
関節リウマチの腱鞘滑膜炎の分子生物学的検討

貝原信孝、山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、岩本幸英

第51回日本リウマチ学会総会・学術集会 2007.4

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Venue：横浜市　平成19年4月26-29日 Country：Japan
膠原病に伴う距骨下関節脱臼の2例

福士純一、中島康晴、光安廣倫、馬渡太郎、岡崎賢、山田久方、貝原信孝、前田健、岩本幸英

第51回日本リウマチ学会総会・学術集会 2007.9

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Venue：横浜市　平成19年4月26-29日 Country：Japan
生物学的製剤による加重関節破壊抑制効果の検討

中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、貝原信孝、前田健、岩本幸英

第51回日本リウマチ学会総会・学術集会 2007.4

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Venue：横浜市　平成19年4月26-29日 Country：Japan
関節リウマチの腱鞘滑膜炎の病理学的、分子生物学的検討

貝原信孝、山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、堀亜希子、岩本幸英

第80回日本整形外科学会学術集会 2007.5

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Venue：神戸市　平成19年5月24-27日 Country：Japan
Total Larsen scoreを用いたRA加重関節の画像評価

中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、堀亜希子、前田健、吉澤誠司、首藤敏秀、岩本幸英

第34回九州リウマチ学会 2007.9

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Venue：北九州市　平成19年9月8-9日 Country：Japan
QCTを用いた骨粗鬆症評価

馬渡太郎、中島康晴、岡崎賢、福士純一、前田健、首藤敏秀、山田久方、三浦裕正、濱井敏、Keaveny TM、岩本幸英

第34回九州リウマチ学会 2007.9

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Venue：北九州市　平成19年9月8-9日 Country：Japan
関節リウマチにおけるIL-17産生T細胞の解析

山田久方、中島康晴、岡崎賢、馬渡太郎、福士純一、岩本幸英

第22回日本整形外科学会基礎学術集会 2007.10

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Venue：浜松市　平成19年10月25-26日 Country：Japan
Identification of IL-17-producing T cells in rheumatoid arthritis

Hisakata Yamada and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Critical role of CD30 ligand / CD30 in controlling inflammatory bowel diseases in mice

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard Podack and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Roles of a novel dual specificity phosphatase, DUSP16, in the development and functions of CD8+ T cells

Momoe Itsumi, Hisakata Yamada, Tetsuya Matsuguchi, and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
TLR-4-dependent cell surface molecule is required for IL-17 production by γδ T cells in the presence of IL-23

Kensuke Shibata, Hisakata Yamada, Risa Nakamura, and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Soluble branched (1,4)-β-D-glucans from Xanthomonas canpestris enhance antitumor activity against murine malignant melanoma through augmented NK activity and cytotoxic T-cell response

Ario Takeuchi, Hisakata Yamada, Yoriyuki Kamiryou, Seiji Naito, and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Tyk2 is indispensable for IL-17 production by peritoneal γδ T cells induced by Escherichia coli infection

Risa Nakamura, Kensuke Shibata, Hisakata Yamada, and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Roles of CD30L in CD4+ and CD8+T cell responses against Mycobacterium bovis Bacillus Calmette-Guérin Infection.

Ce Tang, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Eckhard R. Podack and Yasunobu Yoshikai

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Roles of CD30 ligand in primary infection with L.monocytogenes

WASHITOU Minori, YAMADA Hisakata , ITSUMI momoe ,　OIMOMI hideki , MUTA Hiromi, YOSHIKAI yasunobu

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
Tyk2 in IL-23-mediated signaling is indispensable for the development of experimental autoimmune encephalomyelitis.

Akiko Hori, Hiori Ikebe, Keiichi Nakayama, Yasunobu Yoshikai, and Hisakata Yamada

第37回日本免疫学会 2007.11

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Venue：東京都　平成19年11月20-22日 Country：Japan
関節リウマチにおけるIL-17産生T細胞の解析 Invited

山田久方

第12回リウマチフォーラム 2008.1

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Venue：東京都　平成20年1月19-20日 Country：Japan
生物学的製剤によるRAの関節破壊抑制効果の検討

中島康晴、岡崎賢、馬渡太郎、福士純一、山田久方、堀亜希子、首藤敏秀、岩本幸英

第34回九州リウマチ学会 2008.3

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Venue：北九州市　平成20年3月15-16日 Country：Japan
Notch-IL-7Ra経路は自然発生IL-17産生γδT細胞分化に必須である

中村真隆, 柴田健輔, 山田久方, 吉開泰信

第23回日本生体防御学会学術総会 2012.7

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Language：Japanese

Country：Japan
Notch,γδTCRシグナルによるγδT細胞機能分化制御

柴田健輔, 中村真隆, 山田久方, 吉開泰信

第23回日本生体防御学会学術総会 2012.7

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Country：Japan
クロレラ熱水抽出物の摂取が健常人の免疫機能に及ぼす影響

野口直人, 山田久方, 上野すぎ, 中嶋裕也, 隈本正一郎, 丸山功, 安藤洋太郎, 吉開泰信

第23回日本生体防御学会学術総会 2012.7

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Country：Japan
Notch-RBP-Jk-IL-7 receptor alpha axis is essential for the maintenance of IL-17 producing γδ T cells

Kensuke Shibata, Masataka Nakamura, HISAKATA YAMADA, Koichi Ikuta, Yasunobu Yoshikai

第41回日本免疫学会総会・学術集会 2012.12

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Country：Japan
IL-21 plays an important role in host defence against chronic bacterial infection.

Risa Nakamura, Yinxia Huang, Yojiro Arimori, Naoya Ohara, HISAKATA YAMADA, Yasunobu Yoshikai

第41回日本免疫学会総会・学術集会 2012.12

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Country：Japan
The critical role of CD30L/CD30 signaling in the pathogenesis of experimental autoimmune encephalomyelitis.

Koji Shinoda, Xun Sun, HISAKATA YAMADA, Kensuke Shibata, Junnichi Kira, Yasunobu Yoshikai

第41回日本免疫学会総会・学術集会 2012.12

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Country：Japan
IL-21 plays critical roles in the production of pathogenic autoantibody in a murine model of autoimmune arthritis

HISAKATA YAMADA, Koji Sakuraba, Akiko Oyamada, Risa Nakamura, Kenjiro Fujimura, Yasunobu Yoshikai

第41回日本免疫学会総会・学術集会 2012.12

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Country：Japan
IL-21シグナルはコラーゲン誘導関節炎の発症に重要な役割を果たす

櫻庭康司, 小山田亜希子, 藤村謙次郎, 橋口智光, 岩本幸英, 吉開泰信, 山田久方

第57回日本リウマチ学会総会・学術集会 2013.4

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Country：Japan
CD30 ligand is a target for a novel biological therapy against experimental autoimmune encephalomyelitis

Koji Shinoda, Xun Sun, Akiko Oyamada, HISAKATA YAMADA, Jun-ichi Kira, Yasunobu Yoshikai

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
CD4 T cell tolerance to self type II collagen depends on post-translational modification in the T cell epitope.

HISAKATA YAMADA, Johan Backlund, Rikard Holmdahl, Yasunobu Yoshikai

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
A novel role of CD30L/CD30 signaling by naturally occurring IL-17A-producing γδ T cells in response against mycobacterium bovis BCG.

Ying Guo, Xun Sun, Kensuke Shibata, HISAKATA YAMADA, Hiromi Muta, Eckhard R. Podack, Yasunobu Yoshikai

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
Notch-RBP-Jk-IL-7Rα pathway plays a pivotal role in the maintenance of IL-17-producing γδ T cells.

Masataka Nakamura, Kensuke Shibata, HISAKATA YAMADA, Koichi Ikuta, Yasunobu Yoshikai

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
IL-17-producing γδ T cells develop directly from double-negative 2 cells in murine fetal thymus in Bcl11b-dependent manner.

Kensuke Shibata, HISAKATA YAMADA, Masataka Nakamura, Yasunobu Yoshikai

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
Differential requirement of Tyk2 for development of different subsets of CD44high memory phenotype CD4 T cells with Th1 functions.

Tomomitsu Hashiguchi, Koji Sakuraba, Yasunobu Yoshikai, HISAKATA YAMADA

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
Naturally occurring PD-1+ memory phenotype CD8 T cells belong to non-conventonal CD8T cells and are cyclophosphamide-sensitive regulatory T cells.

Koji Sakuraba, Tomomitsu Hashiguchi,, Yasunobu Yoshikai, HISAKATA YAMADA

第42回日本免疫学会総会・学術集会 2013.12

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Country：Japan
サルコイドーシスに難治性の膝関節滑膜炎を来たし、鏡視下滑膜切除が奏功した１例

山田久方, 田代泰隆, 廣瀬毅, 中島康晴, 岡崎賢, 福士純一, 大石正信, 小山田亜希子, 岩本幸英

第58回日本リウマチ学会総会・学術集会 2014.4

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Country：Japan
関節リウマチ滑膜組織培養法の開発

山田久方, 櫻庭康司, 藤村謙次郎, 中島康晴, 岡崎賢, 福士純一, 大石正信, 田代泰隆, 小山田亜希子, 橋口智光, 江崎幸雄, 宮原寿明, 岩本幸英, 吉開泰信

第58回日本リウマチ学会総会・学術集会 2014.4

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Country：Japan
Successful in vitro culture of synovial explants from rheumatoid arthritis at the air-liquid interface.

山田久方, 櫻庭康司, 吉開泰信

第43回日本免疫学会総会・学術集会 2014.12

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Venue：京都市 Country：Japan

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MISC

自己反応性CD8T細胞の生存維持とIL-15

山田久方

2012.1

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
[Th17 cells and human arthritic diseases]

Yamada H.

Nihon Rinsho Meneki Gakkai Kaishi. 2010;33(4):214-21. 2010.8

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Current perspectives on the role of IL-17 in autoimmune disease

Yamada H

J Inflam Res. 2010 Jun;3:33 - 4 2010.6

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ヒトのTh17細胞と病態

山田久方

細胞工学 2010.3

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Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
Th17 cells in human rheumatoid arthritis

Yamada H

Nihon Rinsho Meneki Gakkai Kaishi 2009.8

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Th17/IL-17はヒト関節リウマチの病態に関与しているか

山田久方

分子リウマチ治療 2009.8

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
IL-17とγδ型Tリンパ球

柴田　健輔、山田　久方、吉開　泰信

炎症と免疫 2009.1

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Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
IL-15

山田久方

整形外科 2008.12

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Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
感染防御におけるサイトカインの役割

柴田　健輔、山田　久方、吉開　泰信

小児科診療 2008.12

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IL-17A産生γδ 型Tリンパ球の機能

柴田　健輔、山田　久方、吉開　泰信

医学のあゆみ 2008.7

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Professional Memberships

日本整形外科学会
九州リウマチ学会
日本リウマチ学会
日本生体防御学会
日本臨床免疫学会
日本免疫学会

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Academic Activities

座長（Chairmanship）

第58回日本リウマチ学会総会・学術集会（ Japan ） 2014.4

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Type：Competition, symposium, etc.
座長（Chairmanship）

第57回日本リウマチ学会総会・学術集会（ Japan ） 2013.4

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Type：Competition, symposium, etc.
座長（Chairmanship）

第56回日本リウマチ学会総会・学術集会（ Japan ） 2012.4

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Type：Competition, symposium, etc.
座長（Chairmanship）

第55回日本リウマチ学会総会・学術集会（ Japan ） 2011.7

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Type：Competition, symposium, etc.
座長（Chairmanship）

第22回日本生体防御学会学術総会（ Japan ） 2011.6 - 2011.7

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Type：Competition, symposium, etc.
座長（Chairmanship）

第54回日本リウマチ学会総会・学術集会（ Japan ） 2010.4

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Type：Competition, symposium, etc.

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Research Projects

滑膜常在マクロファージを中心とした関節炎症病態の解析

Grant number：22K09382 2022 - 2024

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
悪性骨軟部腫瘍における薬剤耐性獲得機構の解明

Grant number：25293325 2013 - 2017

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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Authorship：Coinvestigator(s) Grant type：Scientific research funding
関節リウマチにおける自己抗体産生誘導T細胞の解析

Grant number：24591449 2012 - 2015

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
リウマチ性疾患病態におけるTyrosine kinase 2の機能解析

2009

Grants-in-Aid for Scientific Research 平成２０年度リウマチ性疾患調査・研究助成費

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Authorship：Principal investigator Grant type：Competitive funding other than Grants-in-Aid for Scientific Research
ＩＬー１５による免疫反応制御機構

Grant number：20591783 2008 - 2010

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
IL-15による免疫反応制御機構

Grant number：20591783 2008

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
関節炎症性疾患における新規サイトカインレセプターWSX-1の役割

Grant number：17791008 2005 - 2006

Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

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Authorship：Principal investigator Grant type：Scientific research funding

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Class subject

感染制御学

2013.4 - 2013.9 First semester
免疫学

2013.4 - 2013.9 First semester
感染制御学

2012.4 - 2012.9 First semester
免疫学

2012.4 - 2012.9 First semester
感染制御学

2011.4 - 2011.9 First semester
免疫学

2011.4 - 2011.9 First semester
感染制御学

2010.4 - 2010.9 First semester
フローサイトメータ

2010.4 - 2010.9 First semester
免疫学

2010.4 - 2010.9 First semester

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Social Activities

ここまで分かった最新のリウマチ免疫異常

博多リウマチセミナー福岡市 2013.1

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
関節リウマチの最新の病因論

EFFORT Consortium 名古屋市 2012.3

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture
関節炎の免疫学

日向RA-Meering 日向市 2011.8

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
整形外科医のための免疫学

日整会教育研修会福岡市 2011.6

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture
いま話題の関節リウマチの病因論

第11回博多リウマチセミナー福岡市 2010.1

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
何故DMARDの効果減弱が起こるか？

博多リウマチセミナー福岡市 2007.1

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
痛風の最新情報

博多リウマチセミナー福岡市 2006.1

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
リウマチの痛みのメカニズム

博多リウマチセミナー福岡市 2005.1

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop
骨と関節の10年　公開講座

九州大学整形外科九大キャンパス 2004.10

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Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

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Specialized clinical area

Biological Sciences / Medicine, Dentistry and Pharmacy / Basic Medicine / Immunology

Clinician qualification

Specialist

Japan College of Rheumatology（JCR）
Preceptor

Japan College of Rheumatology（JCR）

Year of medical license acquisition

1992