Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yoshinori Fukui Last modified date:2021.10.22

Professor / Division of Immunogenetics / Department of Immunobiology and Neuroscience / Medical Institute of Bioregulation


Papers
1. Kazufumi Kunimura, Yoshinori Fukui, The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development., Int. Immunol., 10.1093/intimm/dxab065, 2021.09.
2. Keisuke Matsubara, Kazufumi Kunimura, Nana Yamane, Ryosuke Aihara, Tetsuya Sakurai, Daiji Sakata, Takehito Uruno, Yoshinori Fukui, DOCK8 dificiency causes a skewing to type 2 immunity in the gut with expansion of group 2 innate lymphoid cells., Biochem. Biophys. Res. Commun., 10.1016/j.bbrc.2021.04.094, 559, 135-140, 2021.06.
3. Yasuhisa Kamikaseda, Takehito Uruno, Kazufumi Kunimura, Akihito Harada, Kuniko Saiki, Kounosuke Oisaki, Daiji Sakata, Takeshi Nakahara, Makiko Kido-Nakahara, Motomu Kanai, Seiji Nakamura, Yasuyuki Oikawa, Masutaka Furue, Yoshinori Fukui, Target inhibition of EPAS1-driven IL-31 production by a small-molecule compound., J. Allergy Clin. Immun., 10.1016/j.jaci.2021.03.029, 148, 633-638, in press, 2021.04.
4. Tetsuya Sakurai, Mutsuko Kunimoto-Niino, Kazufumi Kunimura, Nana Yamane, Daiji Sakata, Ryosuke Aihara, Tomoharu Yasuda, Shigeyuki Yokoyama, Mikako Shirouzu, Yoshinori Fukui, Takehito Uruno, A conserved PI(4,5)P2-binding domain is critical for immune regulatory function of DOCK8., Life Sci. Alliance, 10.26508/lsa.202000873, 4, 4, e202000873, 2021.02.
5. Ryosuke Aihara, Kazufumi Kunimura, Mayuki Watanabe, Takehito Uruno, Nana Yamane, Tetsuya Sakurai, Daiji Sakata, Fusanori Nishimura, Yoshinori Fukui, DOCK8 controls survival of group 3 innate lymphoid cells in the gut through Cdc42 activation. International Immunology, International Immunology, 10.1093/intimm/dxaa066, 33, 149-160, 2021.03.
6. Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, Mitsuyoshi Nakao, Takehiko Yokomizo, Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation., Cellular&Molecular Immunology, 10.1038/s41423-020-00559-7, 18, 1437-1449, 2020.09.
7. Fumiko Okumura, Yuha Fujiki, Nodoka Oki, Kana Osaki, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura, Cul5-type ubiquitin ligase KLHDC1 contributes to the elimination of truncated SELEONS produced by failed UGA/Sec decoding., iScience, 10.1016/j.isci.2020.100970, 23, 3, 100970, 2020.03.
8. Kazufumi Kunimura, Daiji Sakata, Xin Tun, Takehito Uruno, Miho Ushijima, Tomoya Katakai, Akira Shiraishi, Ryosuke Aihara, Yasuhisa Kamikaseda, Keisuke Matsubara, Hirokazu Kanegane, Shinichiro Sawa, Gerard Eberl, Shouichi Ohga, Yasunobu Yoshikai, Yoshinori Fukui, S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches, Cell Rep., 10.1016/j.celrep.2019.10.091, 26, 9, 2823-2834.e7, 2019.11.
9. Daiji Sakata, Takehito Uruno, Keisuke Matsubara, Tsugunobu Andoh, Kazuhiko Yamamura, Yuki Magoshi, Kazufumi Kunimura, Yasuhisa Kamikaseda, Masutaka Furue, Yoshinori Fukui, Selective role of neurokinin B in IL-31-induced itch response in mice, J. Allergy. Clin. Immunol., 10.1016/j.jaci.2019.06.031, 144, 4, 1130-1133.e8, 2019.10, Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by recurrent eczematous legions and intense itch. Itch can be induced by various chemical mediators. Among them, much attention has been paid to interleukin 31 (IL-31) as an AD-associated itch mediator since the discovery of the pruritogenic action of IL-31 in mice. IL-31 is mainly produced by CD4+ T cells and transmits the signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR), both of which are expressed in dorsal root ganglion (DRG) neurons. However, the neuronal mechanism underlying IL-31–induced itch sensation is poorly understood. By analyzing a mouse model for atopic dermatitis, we found that the expression of Tac2, which encodes neurokinin B (NKB), markedly increased in the DRG neurons in response to IL-31. While NKB-deficient mice lost IL-31–induced itch response, scratching behaviors induced by other pruritogens such as histamine, chloroquine and protease-activated receptor 2 (PAR2) agonist were unaffected in the absence of NKB. NKB transmits the signal through neurokinin 3 receptor (NK3R), a G protein-coupled tachykinin receptor. When wild-type mice were pre-treated with NK3R antagonists, IL-31–induced scratching was significantly attenuated, without affecting itch responses induced by other pruritogens. These results indicate that NKB-NK3R axis could be a novel therapeutic target controlling IL-31–induced itch in AD patients..
10. Kazufumi Kunimura, Takehito Uruno, Yoshinori Fukui, DOCK-family proteins : key players in immune surveillance mechanisms, Int. Immunol., 10.1093/intimm/dxz067, 2019.10.
11. Kazuhito Gotou, Takafumi Morisaki, Daiki Setoyama, Katsuhiko Sasaki, Mikako Yagi, Ko Igami, Soichi Mizuguchi, Takeshi Uchiumi, Yoshinori Fukui, Dongchon Kang, Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation, Cell Reports, 10.1016/j.celrep.2018.10.057, 25, 7, 1800-1815.e4, 2018.11, Dendritic cell (DC) maturation induced by Toll-like receptor agonists requires activation of downstream signal transduction and metabolic changes. The endogenous metabolite citrate has recently emerged as a modulator of DC activation. However, the metabolic requirements that support citrate production remain poorly defined. Here, we demonstrate that p32/C1qbp, which functions as a multifunctional chaperone protein in mitochondria, supports mitochondrial metabolism and DC maturation. Metabolic analysis revealed that the citrate increase induced by lipopolysaccharide (LPS) is impaired in p32-deficient DCs. We also found that p32 interacts with dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase [PDH] complex) and positively regulates PDH activity in DCs. Therefore, we suggest that DC maturation is regulated by citrate production via p32-dependent PDH activity. p32-null mice administered a PDH inhibitor show decreased DC maturation and ovalbumin-specific IgG production in vivo, suggesting that p32 may serve as a therapeutic target for DC-related autoimmune diseases. Although mitochondrial metabolic pathways are essential for DC activation, the precise molecular mechanism remains poorly understood. Gotoh et al. show that mitochondrial p32/C1qbp supports dendritic cell metabolism and maturation. In addition, mitochondrial p32 and pyruvate dehydrogenase activity are necessary for DC maturation in vitro and in vivo..
12. Tetsuya Sakurai, Takehito Uruno, Takaaki Tatsuguchi, Kazuhiko Yamamura, Miho Ushijima, Yuko Hattori, Mutsuko Kukimoto-Niino, Chiemi Mishima-Tsumagari, Mayuki Watanabe, Makoto Suematsu, Yoshinori Fukui, Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye, Science Signaling, 10.1126/scisignal.aao4874, 11, 541, 2018.07, Although immune responses are essential to protect the body from infection, they can also harm tissues. Certain tissues and organs, including the eye, constitute specialized microenvironments that locally inhibit immune reactivity. Dedicator of cytokinesis protein 2 (DOCK2) is a Rac-specific guanine nucleotide exchange factor (GEF) that is predominantly found in hematopoietic cells. DOCK2 plays a key role in immune surveillance because it is essential for the activation and migration of leukocytes. DOCK2 mutations cause severe immunodeficiency in humans. We found that DOCK2-mediated Rac activation and leukocyte migration were effectively inhibited by cholesterol sulfate (CS), but not by cholesterol or other sulfated steroids. CS bound to the catalytic domain of DOCK2 and suppressed its GEF activity. Mass spectrometric quantification revealed that CS was most abundantly produced in the Harderian gland, which provides the lipids that form the oily layer of the tear film. Sulfation of cholesterol is mediated by the sulfotransferases SULT2B1b and, to a lesser extent, SULT2B1a, which are produced from the same gene through alternative splicing. By genetically inactivating Sult2b1, we showed that the lack of CS in mice augmented ultraviolet- and antigen-induced ocular surface inflammation, which was suppressed by administration of eye drops containing CS. Thus, CS is a naturally occurring DOCK2 inhibitor and contributes to the generation of the immunosuppressive microenvironment in the eye..
13. Takahiro Tomino, Hirotada Tajiri, Takaaki Tatsuguchi, Takahiro Shirai, Kounosuke Oisaki, Shigeki Matsunaga, Fumiyuki Sanematsu, Daiji Sakata, Tomoharu Yoshizumi, Yoshihiko Maehara, Motomu Kanai, Jean François Cote, Yoshinori Fukui, Takehito Uruno, DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29S mutation, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2018.02.073, 497, 1, 298-304, 2018.02, Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1P29S, has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1P29S. Enforced expression of Rac1P29S induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1P29S. Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1P29S mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1P29S, and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1P29S mutation..
14. Miho Ushijima, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Yasuhisa Kamikaseda, Kazufumi Kunimura, Daiji Sakata, Takaharu Okada, Yoshinori Fukui, The rac activator DOCK2 mediates plasma cell differentiation and IgG antibody production, Frontiers in Immunology, 10.3389/fimmu.2018.00243, 9, FEB, 2018.02, A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR), which triggers activation of B cells and differentiation into plasma cells (PCs). Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab')2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. These results highlight important role of the DOCK2-Rac axis in PC differentiation and IgG antibody responses..
15. Masutaka Furue, K. Yamamura, Makiko Nakahara, Takeshi Nakahara, Yoshinori Fukui, Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis, Allergy: European Journal of Allergy and Clinical Immunology, 10.1111/all.13239, 73, 1, 29-36, 2018.01, Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder associated with skin barrier dysfunction. The lesional skin of AD exhibits T helper 2 (TH2)-deviated immune reactions. Interleukin-31 (IL-31), preferentially produced from TH2 cells, is a potent pruritogenic cytokine, and its systemic and local administration induces scratching behavior in rodents, dogs and monkeys. Recent clinical trials have revealed that administration of an anti-IL-31 receptor antibody significantly alleviates pruritus in patients with AD. In this review, we summarize recent topics related to IL-31 and its receptor with special references to atopic itch..
16. Soh Yamazaki, Yoshihiko Tanaka, Hiromitsu Araki, Akira Kohda, Fumiyuki Sanematsu, Tomoko Arasaki, Xuefeng Duan, Fumihito Miura, Takaharu Katagiri, Ryodai Shindo, Hiroyasu Nakano, Takashi Ito, Yoshinori Fukui, Shogo Endo, Hideki Sumimoto, The AP-1 transcription factor JunB is required for Th17 cell differentiation, Scientific Reports, 10.1038/s41598-017-17597-3, 7, 1, 2017.12, Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development. Junb-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORγt and RORα and reduced expression of Foxp3, a transcription factor known to antagonize RORγt function..
17. Fumihiko Okumura, Akiko Joo-Okumura, Keisuke Obara, Alexander Petersen, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura, Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2, Molecular Biology of the Cell, 10.1091/mbc.E17-07-0450, 28, 24, 3532-3541, 2017.11, Eph receptor tyrosine kinases and their ephrin ligands are overexpressed in various human cancers, including colorectal malignancies, suggesting important roles in many aspects of cancer development and progression as well as in cellular repulsive responses. The ectodomain of EphB2 receptor is cleaved by metalloproteinases (MMPs) MMP-2/MMP-9 and released into the extracellular space after stimulation by its ligand. The remaining membraneassociated fragment is further cleaved by the presenilin-dependent γ-secretase and releases an intracellular peptide that has tyrosine kinase activity. Although the cytoplasmic fragment is degraded by the proteasome, the responsible ubiquitin ligase has not been identified. Here, we show that SOCS box-containing protein SPSB4 polyubiquitinates EphB2 cytoplasmic fragment and that SPSB4 knockdown stabilizes the cytoplasmic fragment. Importantly, SPSB4 down-regulation enhances cell repulsive responses mediated by EphB2 stimulation. Altogether, we propose that SPSB4 is a previously unidentified ubiquitin ligase regulating EphB2-dependent cell repulsive responses..
18. Lauren A. Peters, Jacqueline Perrigoue, Arthur Mortha, Alina Iuga, Won Min Song, Eric M. Neiman, Sean R. Llewellyn, Antonio Di Narzo, Brian A. Kidd, Shannon E. Telesco, Yongzhong Zhao, Aleksandar Stojmirovic, Jocelyn Sendecki, Khader Shameer, Riccardo Miotto, Bojan Losic, Hardik Shah, Eunjee Lee, Minghui Wang, Jeremiah J. Faith, Andrew Kasarskis, Carrie Brodmerkel, Mark Curran, Anuk Das, Joshua R. Friedman, Yoshinori Fukui, Mary Beth Humphrey, Brian M. Iritani, Nicholas Sibinga, Teresa K. Tarrant, Carmen Argmann, Ke Hao, Panos Roussos, Jun Zhu, Bin Zhang, Radu Dobrin, Lloyd F. Mayer, Eric E. Schadt, A functional genomics predictive network model identifies regulators of inflammatory bowel disease, Nature Genetics, 10.1038/ng.3947, 49, 10, 1437-1449, 2017.10, A major challenge in inflammatory bowel disease (IBD) is the integration of diverse IBD data sets to construct predictive models of IBD. We present a predictive model of the immune component of IBD that informs causal relationships among loci previously linked to IBD through genome-wide association studies (GWAS) using functional and regulatory annotations that relate to the cells, tissues, and pathophysiology of IBD. Our model consists of individual networks constructed using molecular data generated from intestinal samples isolated from three populations of patients with IBD at different stages of disease. We performed key driver analysis to identify genes predicted to modulate network regulatory states associated with IBD, prioritizing and prospectively validating 12 of the top key drivers experimentally. This validated key driver set not only introduces new regulators of processes central to IBD but also provides the integrated circuits of genetic, molecular, and clinical traits that can be directly queried to interrogate and refine the regulatory framework defining IBD..
19. Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui, Corrigendum to “Thymic epithelial cell-specific deletion of Jmjd6 reduces aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes” [Biochemical and Biophysical Research Communications 489/1 (2017) 8–13] (S0006291X1730997X) (10.1016/j.bbrc.2017.05.113), Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2017.08.003, 491, 4, 2017.09, The authors regret to say that they found a minor mistake in their article..
20. Markus Ackerknecht, Kathrin Gollmer, Philipp Germann, Xenia Ficht, Jun Abe, Yoshinori Fukui, Jim Swoger, Jorge Ripoll, James Sharpe, Jens V. Stein, Antigen availability and DOCK2-driven motility govern CD4+ t cell interactions with dendritic cells in vivo, Journal of Immunology, 10.4049/jimmunol.1601148, 199, 2, 520-530, 2017.07, Parenchymal migration of naive CD4+ T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kg and is widely assumed to facilitate efficient screening of dendritic cells (DCs) presenting peptide-MHCs (pMHCs). Yet how CD4+ T cell motility, DC density, and pMHC levels interdependently regulate such interactions has not been comprehensively examined. Using intravital imaging of reactive LNs in DC-immunized mice, we show that pMHC levels determined the occurrence and timing of stable CD4+ T cell-DC interactions. Despite the variability in interaction parameters, ensuing CD4+ T cell proliferation was comparable over a wide range of pMHC levels. Unexpectedly, decreased intrinsic motility of DOCK22/2 CD4+ T cells did not impair encounters with DCs in dense paracortical networks and, instead, increased interaction stability, whereas PI3Kg deficiency had no effect on interaction parameters. In contrast, intravital and whole-organ imaging showed that DOCK2-driven T cell motility was required to detach from pMHClow DCs and to find rare pMHChigh DCs. In sum, our data uncover flexible signal integration by scanning CD4+ T cells, suggesting a search strategy evolved to detect low-frequency DCs presenting high cognate pMHC levels..
21. Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui, Thymic epithelial cell–specific deletion of Jmjd6 reduces Aire protein expression and exacerbates disease development in a mouse model of autoimmune diabetes, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2017.05.113, 489, 1, 8-13, 2017.07, Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity. Here we report that TEC-specific deletion of Jmjd6 exacerbates development of autoimmune diabetes in a mouse model, which express both ovalbumin (OVA) under the control of the rat insulin gene promoter and OT-I T cell receptor specific for OVA peptide bound to major histocompatibility complex class I Kb molecules. We found that Aire protein expression in mTECs was reduced in the absence of Jmjd6, with retention of intron 2 in Aire transcripts. Our results thus demonstrate the importance of Jmjd6 in establishment of immunological tolerance in a more physiological setting..
22. Hirotada Tajiri, Takehito Uruno, Takahiro Shirai, Daisuke Takaya, Shigeki Matsunaga, Daiki Setoyama, Mayuki Watanabe, Mutsuko Kukimoto-Niino, Kounosuke Oisaki, Miho Ushijima, Fumiyuki Sanematsu, Teruki Honma, Takaho Terada, Eiji Oki, Senji Shirasawa, Yoshihiko Maehara, Dongchon Kang, Jean François Côté, Shigeyuki Yokoyama, Motomu Kanai, Yoshinori Fukui, Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1, Cell Reports, 10.1016/j.celrep.2017.04.016, 19, 5, 969-980, 2017.05, Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl-2(1H)-pyridone (TBOPP) as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion..
23. Audrey Le Floc'h, Yoshihiko Tanaka, Niels S. Bantilan, Guillaume Voisinne, Grégoire Altan-Bonnet, Yoshinori Fukui, Morgan Huse, Correction
Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse [The Journal of Experimental Medicine, 210, 12, November 18, (2013) 2721-2737]doi 10.1084/jem.20131324, Journal of Experimental Medicine, 10.1084/jem.2013132403102017c, 214, 4, 2017.04, The authors regret that in the original version of their paper, the middle blot for Rac2 in Fig. 2 C was incorrect. The legend remains correct, and the corrected figure appears below. The online HTML and PDF versions of this article have been corrected. The error only remains in the print version..
24. Akira Shiraishi, Takehito Uruno, Fumiyuki Sanematsu, Miho Ushijima, Daiji Sakata, Toshiro Hara, Yoshinori Fukui, DOCK8 protein regulates macrophage migration through Cdc42 protein activation and LRAP35a protein interaction, Journal of Biological Chemistry, 10.1074/jbc.M116.736306, 292, 6, 2191-2202, 2017.02, DOCK8 is an atypical guanine nucleotide exchange factor for Cdc42, and its mutations cause combined immunodeficiency in humans. Accumulating evidence indicates that DOCK8 regulates the migration and activation of various subsets of leukocytes, but its regulatory mechanism is poorly understood. We here report that DOCK8-deficient macrophages exhibit a migration defect in a 2D setting. Although DOCK8 deficiency in macrophages did not affect the global Cdc42 activation induced by chemokine stimulation, rescue experiments revealed that the guanine nucleotide exchange factor activity of DOCK8 was required for macrophage migration. We found that DOCK8 associated with LRAP35a, an adaptor molecule that binds to the Cdc42 effector myotonic dystrophy kinase-related Cdc42-binding kinase, and facilitated its activity to phosphorylate myosin II regulatory light chain. When this interaction was disrupted in WT macrophages, they showed a migration defect, as seen in DOCK8-deficient macrophages. These results suggest that, during macrophage migration, DOCK8 links Cdc42 activation to actomyosin dynamics through the association with LRAP35a..
25. Kazuhiko Yamamura, Takehito Uruno, Akira Shiraishi, Yoshihiko Tanaka, Miho Ushijima, Takeshi Nakahara, Mayuki Watanabe, Makiko Kido-Nakahara, Ikuya Tsuge, Masutaka Furue, Yoshinori Fukui, The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction, Nature communications, 10.1038/ncomms13946, 8, 2017.01, Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4+ T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4+ T cells abrogates skin disease development in DOCK8-deficient mice. Although EPAS1 is known to form a complex with aryl hydrocarbon receptor nuclear translocator (ARNT) and control hypoxic responses, EPAS1-mediated Il31 promoter activation is independent of ARNT, but in collaboration with SP1. On the other hand, we find that DOCK8 is an adaptor and negative regulator of nuclear translocation of EPAS1. Thus, EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction in CD4+ T cells..
26. Zhiping Liu, Si Ming Man, Qifan Zhu, Peter Vogel, Sharon Frase, Yoshinori Fukui, Thirumala Devi Kanneganti, DOCK2 confers immunity and intestinal colonization resistance to Citrobacter rodentium infection, Scientific reports, 10.1038/srep27814, 6, 2016.06, Food poisoning is one of the leading causes of morbidity and mortality in the world. Citrobacter rodentium is an enteric pathogen which attaches itself to enterocytes and induces attachment and effacing (A/E) lesions. The ability of the bacterium to cause infection requires subversion of the host actin cytoskeleton. Rac-dependent actin polymerization is activated by a guanine nucleotide exchange factor known as Dedicator of cytokinesis 2 (DOCK2). However, the role of DOCK2 in infectious disease is largely unexplored. Here, we found that mice lacking DOCK2 were susceptible to C. rodentium infection. These mice harbored increased levels of C. rodentium bacteria, showed more pronounced weight loss and inflammation-associated pathology, and were prone to bacterial dissemination to the systemic organs compared with wild-type mice. We found that mice lacking DOCK2 were more susceptible to C. rodentium attachment to intestinal epithelial cells. Therefore, our results underscored an important role of DOCK2 for gastrointestinal immunity to C. rodentium infection..
27. Fumihiko Okumura, Keiji Uematsu, Stuart D. Byrne, Mie Hirano, Akiko Joo-Okumura, Akihiko Nishikimi, Taro Shuin, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura, Parallel regulation of von Hippel-Lindau disease by pVHL-mediated degradation of B-Myb and hypoxia-inducible factor α, Molecular and cellular biology, 10.1128/MCB.00067-16, 36, 12, 1803-1817, 2016.06, pVHL, the protein product of the von Hippel-Lindau (VHL) tumor suppressor gene, is a ubiquitin ligase that targets hypoxiainducible factor α (HIF-α) for proteasomal degradation. Although HIF-α activation is necessary for VHL disease pathogenesis, constitutive activation of HIF-α alone did not induce renal clear cell carcinomas and pheochromocytomas in mice, suggesting the involvement of an HIF-α-independent pathway in VHL pathogenesis. Here, we show that the transcription factor B-Myb is a pVHL substrate that is degraded via the ubiquitin-proteasome pathway and that vascular endothelial growth factor (VEGF)- and/or platelet-derived growth factor (PDGF)-dependent tyrosine 15 phosphorylation of B-Myb prevents its degradation. Mice injected with B-Myb knockdown 786-O cells developed dramatically larger tumors than those bearing control cell tumors. Microarray screening of B-Myb-regulated genes showed that the expression of HIF-α-dependent genes was not affected by B-Myb knockdown, indicating that B-Myb prevents HIF-α-dependent tumorigenesis through an HIF-α-independent pathway. These data indicate that the regulation of B-Myb by pVHL plays a critical role in VHL disease..
28. Keiji Uematsu, Fumihiko Okumura, Syunsuke Tonogai, Akiko Joo-Okumura, Dawit Hailu Alemayehu, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura, ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation, Journal of Cell Biology, 10.1083/jcb.201603062, 215, 1, 2016.01, Proper dynamic regulation of the spindle is essential for successful cell division. However, the molecular mechanisms that regulate spindle dynamics in mitosis are not fully understood. In this study, we show that Cullin 5-interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3, a regulator of spindle dynamics, thereby targeting it for proteasomal degradation. The presence of microtubules (MTs) prevented the ASB7-DDA3 interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization and increased the proportion of cells with unaligned chromosomes, and this phenotype was rescued by deletion of DDA3. Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3..
29. Toyoshi Yanagihara, Fumiyuki Sanematsu, Sato T, Takehito Uruno, DUAN XUEFENG, Takahiro Tomino, Yosuke Harada, Mayuki Watanabe, YUQING WANG, Yoshihiko Tanaka, Yoichi Nakanishi, M. Suyama, Yoshinori Fukui, Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus, Nature Commun., 6, 8820, 2015.11.
30. Guo X, Shi N, Cui X-B, Wang J-N, Yoshinori Fukui, Chen S-Y, Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling, Cir. Res. , 116, e71-e80, 2015.05.
31. Abu-Thuraia A, Gauthier R, Chidiac R, Yoshinori Fukui, Screaton RA, Gratton JP, Cote JF, Axl phosphorylates Elmo scraffold proteins to promote Rac activation and cell invasion, Mol. Cell. Biol., 35, 76-87, 2015.01.
32. Watanabe M, Terasawa M, Miyano K, Yanagihara T, 宇留野 武人, Fumiyuki Sanematsu, Cote JF, Hideki Sumimoto, Yoshinori Fukui, DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation, J. Immunol., 193, 5660-5667, 2014.12.
33. Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, Nacher M, Pitaval C, Radovanovic I, Yoshinori Fukui, McEver RP, Filippi M-D, Lizasoain I, Ruiz-Cabello J, Zarbock A, Moro MA, Hidalgo A, Neutrophils scan for activated platelets to initiate inflammation, Science, 346, 1234-1238, 2014.12.
34. Moalli F, Cupovic J, Thelen F, Halbherr P, Yoshinori Fukui, Narumiya S, Ludewig B, Stein JV, Thromboxane A2 acts as tonic immunoregulator by preferential disruption of low-avidity CD4+ T cell-dendritic cell interactions, J. Exp. Med., 211, 2507-2517, 2014.12.
35. Wen Y, Elliott MJ, Huang Y, Miller TO, Corbin DR, Hussain L-R, Ratajczak MZ, Yoshinori Fukui, Ilsars ST, DOCK2 is critical for CD8+TCR- graft facilitating cells to enhance engraftment of hematopoietic stem and progenitor cells, Stem Cells, 32, 2732-2734, 2014.10.
36. Kana Ogawa, Yoshihiko Tanaka, Takehito Uruno, DUAN XUEFENG, Yosuke Harada, Fumiyuki Sanematsu, Kazuhiko Yamamura, 寺澤 公男, Akihiko Nishikimi, JF Côté, Yoshinori Fukui, DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation, J. Exp.Med., 211, 1407-1419, 2014.07, マスト細胞は、細胞内に分泌顆粒を有しており、これに含まれるケミカルメディエーターを細胞外部に放出することで、アナフィラキシーと呼ばれる重篤なアレルギー反応を惹起する。マスト細胞はその表面にIgE抗体の高親和性受容体であるFcεRIを発現しており、これが抗原およびIgE抗体で架橋されると微小管のダイナミックな再構築が誘導され、脱顆粒反応がおこる。しかしながらこれまで、FcεRI近位のシグナル伝達機構に関してよく解析されているものの、微小管動態を制御する遠位のシグナル経路については依然として不明な点が多い。本研究において私達は、Racのグアニンヌクレオチド交換因子 (GEF)であるDOCK5が、マスト細胞の脱顆粒反応を重要な役割を演じていることを示す。私達は、DOCK5欠損マウスが全身性および皮膚アナフィラキシーショックに抵抗性を示すことを見いだした。驚いたことに、DOCK5が持つRac GEFとしての活性は、マスト細胞の脱顆粒反応に必要ではなかった。代わり、DOCK5はNck2やAktと会合し、GSK3βのリン酸化と不活性化を制御することで、微小管動態をコントロールしており、これらの分子との会合をブロックすると、微小管形成や脱顆粒反応が著しく障害された。以上より、DOCK5はアダプターとして機能し、マスト細胞の脱顆粒反応に重要な微小管動態を制御していることを明らかにした。.
37. Damoulakis G, Gambardella L, Rossman K, Lawson C, Anderson K, Yoshinori Fukui, Welch H, Der C, Stephens L, Hawkins P, P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils., J. Cell Sci., 127, 2589-2600, 2014.06.
38. Laurin M, Dumouchel A, Yoshinori Fukui, Côté JF, The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo., Small GTPases , 4, 4, 2013.12.
39. Le Floc’h A, Yoshihiko Tanaka, Bantilan BS, Voisinne G, Altan-Bonnet G, Yoshinori Fukui, Huse M, Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse. , J. Exp. Med., 210, 2721-2737, 2013.11.
40. Akihiko Nishikimi, M Kukimoto-Niino, S Yokoyama, Yoshinori Fukui, Immune regulatory functions DOCK family proteins in health and disease., Exp.Cell.Res., 319, 15, 2343-2349, 2013.09.
41. Sachiko Kamakura, Masatoshi Nomura, Jyunya Hayase, Y Iwakiri, Akihiko Nishikimi, Ryoichi Takayanagi, Yoshinori Fukui, Hideki Sumimoto, The cell polarity protein mlnsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway., Dev. Cell., 26, 3, 292-302, 2013.08.
42. Yusuke Sakai, Yoshihiko Tanaka, Tohoshi Yanagihara, Mayuki Watanabe, DUAN XUEFENG, 寺澤 公男, Akihiko Nishikimi, Fumiyuki Sanematsu, Yoshinori Fukui, The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation., Blood, 122, 3, 386-393, 2013.05.
43. M Laurin, J Huber, A Pelletier, T Houalla, M Park, Yoshinori Fukui, B Haibe-Kains, WJ Muller, JF Côté, Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis., Proc.Natl.Acad.Sci.USA, 110, 18, 7434-7439, 2013.03.
44. Cimino PJ, Yang Y, Li X, Hemingway JF, Cherne MK, Khademi SB, Fukui Y, Montine KS, Montine TJ, Keene CD, Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of alzheimer's disease, Exp. Mol. Pathol., 10.1016/j.yexmp.2013.01.002., in press, 1-5, 2013.01.
45. Unoki M, Masuda A, Dohmae N, Arita K, Yoshimatsu M, Iwai Y, Fukui Y, Ueda K, Hamamoto R, Shirakawa M, Sasaki H, Nakamura Y, Lysyl 5-Hydroxylation, a novel histone modification, by jumonji domain containing 6(JMJD6), J. Biol. Chem., in press, 1-5, 2013.01.
46. Fumiyuki Sanematsu, Akihiko Nishikimi, Mayuki Watanabe, T Hongu, Yoshihiko Tanaka, Y Kanaho, JF Côté, Yoshinori Fukui, Phosphatidic acid-dependent recruitment and function of the Rat activator DOCK1 during dorsal ruffle formation, J. Biol. Chem., 288, 8092-8100, 2013.01.
47. Shigeo Fujimori, Naoya Hirai, Hiroyuki Ohashi, Kazuyo Masuoka, Akihiko Nishikimi, Yoshinori Fukui, Takanori Washio, Tomohiro Oshikubo, Tatsuhiro Yamashita, Etsuko Miyamoto-Sato, Next-generation sequencing coupled with a cell-free display technology for high-throughput production of reliable interactome data, Scientific Reports, 10.1038/srep00691, 2:691, 1-5, 2012.10.
48. Masao Terasawa, Takehito Uruno, Sayako Mori, Mutsuko Kukimoto-Niino, Akihiko Nishikimi, Fumiyuki Sanematsu, Yoshihiko Tanaka, Shigeyuki Yokoyama, Yoshinori Fukui, Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration, PLoS One, 2012.09.
49. Nishikimi A, Uruno T, Duan X, Cao Q, Okamura Y, Saitoh N, Sakaoka S, Du Y, Suenaga A, Kukimoto-NIino M, Miyano K, Okabe T, Sanematsu F, Tanaka Y, Sumimoto H, Honma T, Yokoyama S, Nagano T, Kohda D, Kanai M, Fukui Y, Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2., Chem. Biol., 19, 488-497, 2012.04.
50. Harada Y, Tanaka Y, Terasawa M, Pieczyk M, Habiro K, Katakai T, Hanawa-Suetsugu K, Kukimoto-Niino M, Nishizaki T, Shirousu M, Duan X, Uruno T, Nishikimi A, Sanematsu F, Yokoyama S, Stein JV, Kinashi T, Fukui Y , DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses, Blood, 119, 4451-4461, 2012.03, 樹状細胞は、抗原に暴露されると輸入リンパ管を介してリンパ節に移動し、T 細胞に抗原を提示することで免疫応答を惹起する。樹状細胞は、三次元微小環境下では、二次元環境と異なり、インテグリン非依存的に細胞外マトリックスの隙間を形を変えながら進んでいくが、このアメーバ様運動を制御するシグナル伝達機構やスペースを感知するメカニズムは明らかではない。私達は、ヒト免疫不全症の責任分子として近年注目を集めているDOCK8の機能を、ノックアウトマウスを作製することで解析した。その結果、DOCK8欠損樹状細胞ではリンパ節へのホーミングが障害されており、T細胞を効率よく活性化できないことを見いだした。DOCK8欠損樹状細胞は二次元環境では正常に運動できるにも関わらず、三次元微小環境下での運動が顕著に障害されていた。DOCK8はCdc42特異的なGEFとして機能しており、その複合体の構造を決定すると共に、FRETを用いて、DOCK8がCdc42活性化の場の制御に重要な役割を演じることを明らかにした。.
51. Hanawa-Suetugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinishi T, Kohda D, Fukui Y, Yokoyama S, Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms., Proc. Natl. Acad. Sci. USA, 109, 9, 3305-3310, 2012.02.
52. Ippagunta SK, Subbarao Malireddi RK, Shaw PJ, Neal GA, Walle LV, Green DR, Fukui Y, Lamkanfi M, Kanneganti T-D, The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization., Nature Immunology, 2011.09.
53. Sanematsu F, Hirashima M, Laurin M, Takii R, Nishikimi A, Kitajima K, Ding G, Noda M, Murata Y, Tanaka Y, Masuko S, Suda T, Meno C, Côté JF, Nagasawa T, Fukui Y, DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4., Circ. Res., 107:1102-1105, 2010.10.
54. Boscacci RT, Pfeiffer F, Gollmer K, Checa Sevilla AC, Martin AM, Soriano SF, Natale D, Henrickson SE, Andrian UH, Fukui Y, Mellado M, Deutsch U, Engelhardt B, Stein JV, Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and non-redundant roles for ICAM-1, ICAM-2, VCAM-1 in lymphocyte homing, Blood, 116: 915-925, 2010.08.
55. Kumar V, Scandella E, Danuser R, Onder L, Nitschke M, Fukui Y, Halin C, Ludewig B, Stein JV, Global lymphoid tissue remodeling during a viral infection is orchestrated by a B-cell-lymphotoxin-dependent pathway, Blood, 115: 4725-4733, 2010.06.
56. Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, Ishikawa T, Hoshino K, Uruno T, Cao Q, Higashi S, Kawaguchi Y, Enjoji M, Takayanagi R, Kaisho T, Yoshikai Y, Fukui Y, Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation, J. Exp. Med., 207: 721-730, 2010.04, 形質細胞様樹状細胞(pDC)は、微生物由来の核酸を細胞内に存在するTLR7/TLR9を介して認識することで、炎症性サイトカインのみならず、大量のI型インターフェロン(IFN)を産生することから、近年脚光を集めている細胞である。pDC活性化におけるDOCK2の役割を解析する目的で、種々のTLRリガンドでpDCを刺激したところ、DOCK2欠損pDCではIL-12p40、IL-6といった炎症性サイトカインは正常に産生されるにも関わらず、I型IFNの産生が著しく低下することを見出した。このメカニズムを詳細に解析することで、TLRによる抗原認識とは独立してDOCK2-Racシグナル伝達系が作動し、IKK-alphaの活性化を介して、I型IFN産生を選択的に制御するという、新しい制御機構の存在を明らかにした。.
57. Lei Y, Liu C, Saito F, Fukui Y, Takahama Y, Role of DOCK2 and DOCK180 in fetal thymus colonization, Eur. J. Immunol., 39 : 2695-2702, 2009.09.
58. Cimino PJ, Sokal I, Leverenz J, Fukui Y, Montine TJ, DOCK2 is a Microglial Specific Regulator of Central Nervous System Innate Immunity Found in Normal and Alzheimer's Disease Brain, Am. J. Pathol., 175 : 1622-1630, 2009.09.
59. Nagatake T, Fukuyama S, Kim DY, Goda K, Igarashi O, Sato S, Nochi T, Sagara H, Yokota Y, Jetten AM, Kaisho T, Akira A, Mimuro H, Sasakawa C, Fukui Y, Fujihashi K, Akiyama T, Inoue J, Enninger JM, Kunisawa J, Kiyono H, Id2-, RORγt-, and LTβR-independent lymphoid organogenesis in ocular immunity, J. Exp. Med., 206 : 2351-2364, 2009.09.
60. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, Cao Q, Sanematsu F, Kanai M, Hasegawa H, Tanaka Y, Shibasaki M, Kanaho Y, Sasaki T, Frohman MA, Fukui Y, , Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis, Science, 324:384-387, 2009.04.
61. Gollmer K, Asperti-Boursin F, Tanaka Y, Okkenhaug K, Vanhaesebroeck B, Peterson JR, Fukui Y, Donnadieu E, Stein JV, CCL21 mediates CD4+ T cell costimulation via a DOCK2/Rac-dependent pathway, Blood, 114(3) : 580-588, 2009.03.
62. Nakasaki T, Tanaka T, Okudaira S, Hirosawa M, Umemoto E, Otani K, Jin S, Bai Z, Hayasaka F, Fukui Y, Aozasa K, Fujita N, Tsuruo T, Ozono K, Aoki J, Miyasaka M, Involvement of lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions, Am. J. Pathol., 173, 1566-1576, 2008.10.
63. Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y, Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells, Blood, 111(6), 2973-2976, 2008.03.
64. Kikuchi T, Kubonishi S, Shibakura M, Namba N, Matui T, Fukui Y, Tanimoto M, Katayama Y, Dock2 participates in bone marrow lympho-hematopoiesis, Biochem. Biophys. Res. Commun., 367: 90-96, 2008.01.
65. Higuchi N, Kato M, Kotoh K, Kohjima M, Aishima S, Nakamuta M, Fukui Y, Takayanagi R, Enjoji M, Methylprednisolone injection via the portal vein suppresses inflammation in acute liver failure induced in rats by lipopolysaccharide and d-galactosamine, Liver Int., 27: 1342-1348, 2007.12.
66. Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, Takii R, Kawaguchi M, Inayoshi A, Masuko S, Himeno K, Sasazuki T, Fukui Y, T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2., Nature Immunol., 8,1067-1075, 2007.09.
67. Nombela-Arrieta C, Mempel TR, Soriano SF, Mazo I, Wymann MP, Hirsch E, Martínez-A C, Fukui Y, von Andrian UH, Stein JV, A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediatsd egress, J. Exp. Med., 9: 121-128, 2007.03.
68. Handa Y, Suzuki M, Ohya K, Iwai H, Ishijima N, Koleske AJ, Fukui Y, Sasakawa C, Shignella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery., Nature Cell Biology, 9: 121-128, 2007.01.
69. García-Bernal D, Sotillo-Mallo E, Nombela-Arrieta C, Samaniego R, Fukui Y, Stein JV, Teixidó J, DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1., J. Immunol., 177: 5215-5225, 2006.10.
70. Kunisaki Y, Nishikimi A, Tanaka Y, Takii R, Noda M, Inayoshi A, Watanabe K, Sanematsu F, Sasazuki T, Sasaki T, Fukui Y, DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis., J. Cell Biol., 174: 647-652, 2006.04.
71. Kunisaki Y, Tanaka Y, Sanui T, Inayoshi A, Noda M, Nakayama T, Harada M, Taniguchi M, Sasazuki T, Fukui Y, DOCK2 is required in T cell precursors for development of Valpha14 natural killer T (NKT) cells., J. Immunol., 176: 4640-4645, 2006.04.
72. Shulman Z, Pasvolsky R, Woolf E, Grabovsky V, Feigelson SW, Erez N, Fukui Y, Alon R, DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration., Blood, 108: 2150-2158, 2006.04.
73. Jiang H, Pan F, Erickson LM, Jang MS, Sanui T, Kunisaki Y, Sasazuki T, Fukui Y, Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection, J. Exp. Med, 10.1084/jem.20050911, 202, 8, 1121-1130, 202: 1121-1130, 2005.10.
74. Nombela-Arrieta C, Lacalle RA, Montoya M, Kunisaki Y, Megilas D, Marques M, Carrera AC, Manes S, Fukui Y, Martines-A C, Stein JV, Differential requirements of DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing, Immunity, 10.1016/j.immuni.2004.07.012, 21, 3, 429-441, 21: 429-441, 2004.09.
75. Kunisaki T, Masuko S, Noda M, Inayoshi A, Sanui T, Harada M, Sasazuki T, Fukui Y., Defective fetal liver erythropoiesis and T-lymphopoiesis in mice lacking phosphatidylserine receptor, Blood, 10.1182/blood-2003-09-3245, 103, 9, 3362-3364, 103:119-129, 2004.05.
76. Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, Fukui Y, DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-q and LFA-1, in T cells, Immunity, 10.1016/S1074-7613(03)00169-9, 19, 1, 119-129, 19:119-129, 2003.01.
77. Sanui T, Inayoshi A, Noda M, Iwata E, Stein JV, Sasazuki T, Fukui Y, DOCK2 regulates Rac activation and cytoskeletal reorganization through the interaction with ELMO1, Blood, 10.1182/blood-2003-01-0173, 102, 8, 2948-2950, 102: 2948-2950, 2003.01.
78. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, Inayoshi A, Noda M, Oike M, Shirai T, Sasazuki T, Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration, Nature, 10.1038/35090591, 412, 6849, 826-831, 412: 826-831, 2001.01.
79. Oono T, Fukui Y, Masuko S, Hashimoto O, Ueno T, Sanui T, Inayoshi A, Noda M, Sata M, Sasazuki T, Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide., J. Clin. Invest, 10.1172/JCI13256, 108, 11, 1589-1596, 108: 1589-1596, 2001.01.
80. Kawamura K, Yamamura T, Yokoyama K, Chui DH, Fukui Y, Sasazuki T, Inoko H, David CD, Tabira T:, HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice, J. Clin. Invest, 10.1172/JCI8407, 105, 7, 977-984, 105:977-984, 2000.01.
81. Fukui Y, Oono T, Cabaniols JP, Nakao K, Hirokawa K, Inayoshi A, Sanui T, Kanellopoulos J, Iwata E, Noda M, Katsuki M, Kourilsky P, Sasazuki T, Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor-contact., Proc. Natl. Acad. Sci. USA, 10.1073/pnas.250470797, 97, 25, 13760-13765, 97:13760-13765, 2000.01.
82. Matsuki N, Ogasawara K, Takami K, Namba K, Takahashi A, Fukui Y, Sasazuki T, Iwabuchi K, Good RA, Onoe K, Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory, Vaccine, 10.1016/S0264-410X(98)00336-3, 17, 9-10, 1161-1168, 17: 1161-1168, 1999.01.
83. Sano T, Yamamoto K, Fukui Y, Sasazuki T, Spontaneous clustering of Thy-1 antigens on CD4+ CD8+ thymocytes lacking TCR engagement by MHC/peptide complexes, Eur. J. Immunol, 10.1002/(SICI)1521-4141(199902)29:02<403::AID-IMMU403>3.3.CO;2-T, 29, 2, 403-412, 29:403-412, 1999.01.
84. Nishimura H, Washizu J, Naiki Y, Hara T, Fukui Y, Sasazuki T, Yoshikai Y, MHC class II-dependent NK1.1+gd T cells are induced in mice by Salmonella infection, J. Immunol, 162, 3, 1573-1581, 162:1573-1581, 1999.01.
85. Gyotoku T, Fukui Y, Sasazuki T, An endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability., Eur. J. Immunol., 10.1002/(SICI)1521-4141(199812)28:12<4050::AID-IMMU4050>3.3.CO;2-P, 28, 12, 4050-4061, 28:4050-4061, 1998.01.
86. Takahashi A, Ogasawara K, Matsuki N, Fujinaga K, Nakaya T, Ikuta K, Auwanit W, Honda M, Fukui Y, Sasazuki T, Iwabuchi K, Ono K, Development of peptide vaccines inducing production of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice, Vaccine, 10.1016/S0264-410X(98)00042-5, 16, 16, 1537-1543, 16: 1537-1543, 1998.01.
87. Fukui Y, Hashimoto O, Inayoshi A, Gyotoku T, Sano T, Koga T, Gushima T, Sasazuki T, Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor b chain., J. Exp. Med., 10.1084/jem.188.5.897, 188, 5, 897-907, 188:897-907, 1998.01.
88. Gapin L, Fukui Y, Kanellopoulos J, Sano T, Casrouge A, Malier V, Beaudoing E, Gautheret D, Claverie JM, Sasazuki T, Kourilsky P, Quantitative analysis of the T-cell repertoire by a single peptide/MHC complex, J. Exp. Med., 187: 1871-1883, 1998.01.
89. Fukui Y, Ishimoto T, Utsuyama M, Gyotoku T, Koga T, Nakao K, Hirokawa K, Katsuki M, Sasazuki,, Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus, Immunity, 10.1016/S1074-7613(00)80283-6, 6, 4, 401-410, 6: 401-410, 1997.01.
90. Fukui Y, Yamamoto K, Koga T, Yamane K, Sasazuki T, Differential requirement of MHC class II molecules expressed on haematopoietic cells for positive selection of CD4+ thymocytes in TCRαβ and TCRβ transgenic mice. , Int. Immunol., 10.1093/intimm/9.9.1385, 9, 9, 1385-1391, 9:1385-1391, 1997.01.
91. Esaki Y, Fukui Y, Sudo T, Yamamoto K, Inamitsu T, Nishimura Y, Hirokawa K, Kimura A, Sasazuki T, Role of human major histocompatibility complex DQ molecules in superantigenicity of Streptococcus-derived protein. , Infect. Immun., 62, 4, 1228-1235, 62: 1228-1235, 1994.01.
92. Ishimoto T, Yamamoto K, Fukui Y, Fukuda Y, Dohi K, Sasazuki T, In vitro and In vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression. , J. Immunol., 159, 8, 3717-3722, 159: 3717-3722, 1997.01.
93. Takeshita T, Fukui Y, Yamamoto K, Yamane K, Inamitsu T, Kamikawaji N, Sasazuki T, Identification of HLA-DQ6-derived peptide recognized by mouse MHC class I H-2Db-restricted CD8+ T cells in HLA-DQ6 transgenic mice., Jpn. J. Human Genet., 42: 225-232, 1997.01.
94. Yamamoto K, Fukui Y, Esaki Y, Inamitsu T, Sudo T, Yamane K, Kamikawaji N, Kimura A, Sasazuki T, Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice., J. Exp. Med., 10.1084/jem.180.1.165, 180, 1, 165-171, 180: 165-171, 1994.01.
95. Fukui Y, Yamamoto K, Yokoyama N, Iwanaga T, Kurashima C, Esaki Y, Kimura A, Akashi T, Hirokawa K, Sasazuki T, Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in aquisition of T cell tolerance to self-superantigens and procesed DRα-derived peptide., Eur. J. Immunol., 10.1002/eji.1830230742, 23, 7, 1678-1686, 23: 1678-1686, 1993.01.
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