Updated on 2024/08/26

Information

 

写真a

 
ATARASHI KOJI
 
Organization
Faculty of Medical Sciences Department of Basic Medicine Professor
School of Medicine Department of Medicine（Joint Appointment）
Graduate School of Medical Sciences Department of Medicine（Joint Appointment）
Graduate School of Medical Sciences Department of Medical Sciences（Joint Appointment）
Title
Professor
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Research Areas

  • Life Science / Bacteriology

  • Life Science / Immunology

Research History

  • Kyushu University Faculty of Medical Sciences Professor

    2024.4 - Present

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  • 慶應義塾大学医学部 准教授

    2017.2 - 2024.3

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Research Interests・Research Keywords

  • Research theme：Mucosal immunology

    Keyword：Mucosal immunology

    Research period： 2024

  • Research theme：Gut microbiota

    Keyword：Gut microbiota

    Research period： 2024

Papers

  • Periportal macrophages protect against commensal-driven liver inflammation. International journal

    Yu Miyamoto, Junichi Kikuta, Takahiro Matsui, Tetsuo Hasegawa, Kentaro Fujii, Daisuke Okuzaki, Yu-Chen Liu, Takuya Yoshioka, Shigeto Seno, Daisuke Motooka, Yutaka Uchida, Erika Yamashita, Shogo Kobayashi, Hidetoshi Eguchi, Eiichi Morii, Karl Tryggvason, Takashi Shichita, Hisako Kayama, Koji Atarashi, Jun Kunisawa, Kenya Honda, Kiyoshi Takeda, Masaru Ishii

    Nature   2024.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1-5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco+ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco+ macrophages. Functional ablation of Marco+ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco+ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.

    DOI： 10.1038/s41586-024-07372-6

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  • Rationally-defined microbial consortia suppress multidrug-resistant proinflammatory Enterobacteriaceae via ecological control. International journal

    Kenya Honda, Munehiro Furuichi, Takaaki Kawaguchi, Marie-Madlen Pust, Keiko Yasuma-Mitobe, Damian Plichta, Naomi Hasegawa, Takashi Ohya, Shakti Bhattarai, Satoshi Sasajima, Aoto Yoshimasa, Timur Tuganbaev, Mizuki Yaginuma, Masahiro Ueda, Nobuyuki Okahashi, Kimiko Amafuji, Yuuko Kiridooshi, Kayoko Sugita, Martin Stražar, Ashwin Skelly, Wataru Suda, Masahira Hattori, Nobuhiro Nakamoto, Silvia Caballero, Jason Norman, Bernat Olle, Takeshi Tanoue, Makoto Arita, Vanni Bucci, Koji Atarashi, Ramnik Xavier

    Research square   2023.10

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    Persistent colonization and outgrowth of pathogenic organisms in the intestine may occur due to long-term antibiotic usage or inflammatory conditions, which perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, though an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5-7. In this study, we rationally isolated and down-selected commensal bacterial consortia from healthy human stool samples capable of strongly and specifically suppressing intestinal Enterobacteriaceae. One of the elaborated consortia, consisting of 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby reestablishing colonization resistance and alleviating antibiotic-resistant Klebsiella-driven intestinal inflammation in mice. Harnessing these microbial activities in the form of live bacterial therapeutics may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant bacterial infection.

    DOI： 10.21203/rs.3.rs-3462622/v1

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  • Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. International journal

    Joachim Johansen, Koji Atarashi, Yasumichi Arai, Nobuyoshi Hirose, Søren J Sørensen, Tommi Vatanen, Mikael Knip, Kenya Honda, Ramnik J Xavier, Simon Rasmussen, Damian R Plichta

    Nature microbiology   8 ( 6 )   1064 - 1078   2023.6

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    Distinct gut microbiome ecology may be implicated in the prevention of aging-related diseases as it influences systemic immune function and resistance to infections. Yet, the viral component of the microbiome throughout different stages in life remains unexplored. Here we present a characterization of the centenarian gut virome using previously published metagenomes from 195 individuals from Japan and Sardinia. Compared with gut viromes of younger adults (>18 yr) and older individuals (>60 yr), centenarians had a more diverse virome including previously undescribed viral genera, such as viruses associated with Clostridia. A population shift towards higher lytic activity was also observed. Finally, we investigated phage-encoded auxiliary functions that influence bacterial physiology, which revealed an enrichment of genes supporting key steps in sulfate metabolic pathways. Phage and bacterial members of the centenarian microbiome displayed an increased potential for converting methionine to homocysteine, sulfate to sulfide and taurine to sulfide. A greater metabolic output of microbial hydrogen sulfide in centenarians may in turn support mucosal integrity and resistance to pathobionts.

    DOI： 10.1038/s41564-023-01370-6

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  • Diet-mediated constitutive induction of novel IL-4+ ILC2 cells maintains intestinal homeostasis in mice International journal

    Wanlin Cui, Yuji Nagano, Satoru Morita, Takeshi Tanoue, Hidehiro Yamane, Keiko Ishikawa, Toshiro Sato, Masato Kubo, Shohei Hori, Tadatsugu Taniguchi, Masanori Hatakeyama, Koji Atarashi, Kenya Honda

    Journal of Experimental Medicine   220 ( 8 )   2023.5   （ ISSN:0022-1007 eISSN:1540-9538 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Rockefeller University Press  

    Group 2 innate lymphoid cells (ILC2s) expressing IL-5 and IL-13 are localized at various mucosal tissues and play critical roles in the induction of type 2 inflammation, response to helminth infection, and tissue repair. Here, we reveal a unique ILC2 subset in the mouse intestine that constitutively expresses IL-4 together with GATA3, ST2, KLRG1, IL-17RB, and IL-5. In this subset, IL-4 expression is regulated by mechanisms similar to but distinct from those observed in T cells and is partly affected by IL-25 signaling. Although the absence of the microbiota had marginal effects, feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4+ ILC2s. The decrease in the number of IL-4+ ILC2s caused by the vitamin B1 deficiency was accompanied by a reduction in IL-25–producing tuft cells. Our findings reveal that dietary vitamin B1 plays a critical role in maintaining interaction between tuft cells and IL-4+ ILC2s, a previously uncharacterized immune cell population that may contribute to maintaining intestinal homeostasis.

    DOI： 10.1084/jem.20221773

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  • An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development. International journal

    Chia-Wen Lin, Jacob Ellegood, Kota Tamada, Ikuo Miura, Mikiko Konda, Kozue Takeshita, Koji Atarashi, Jason P Lerch, Shigeharu Wakana, Thomas J McHugh, Toru Takumi

    Molecular psychiatry   28 ( 5 )   1932 - 1945   2023.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    The BTBR T+Itpr3tf/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.

    DOI： 10.1038/s41380-023-01999-z

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  • Myeloid-like B cells boost emergency myelopoiesis through IL-10 production during infection International journal

    Masashi Kanayama, Yuta Izumi, Megumi Akiyama, Toyoki Hayashi, Koji Atarashi, Axel Roers, Taku Sato, Toshiaki Ohteki

    Journal of Experimental Medicine   220 ( 4 )   2023.1   （ ISSN:0022-1007 eISSN:1540-9538 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Rockefeller University Press  

    Emergency myelopoiesis (EM) is a hematopoietic response against systemic infections that quickly supplies innate immune cells. As lymphopoiesis is strongly suppressed during EM, the role of lymphocytes in that process has not received much attention. Here, we found that myeloid-like B cells (M-B cells), which express myeloid markers, emerge in the bone marrow (BM) after the induction of EM. M-B cells were mainly derived from pre-B cells and preferentially expressed IL-10, which directly stimulates hematopoietic progenitors to enhance their survival and myeloid-biased differentiation. Indeed, lacking IL-10 in B cells, blocking IL-10 in the BM with a neutralizing antibody, and deleting the IL-10 receptor in hematopoietic progenitors significantly suppressed EM, which failed to clear microbes in a cecal ligation and puncture model. Thus, a distinct B cell subset generated during infection plays a pivotal role in boosting EM, which suggests the on-demand reinforcement of EM by adaptive immune cells.

    DOI： 10.1084/jem.20221221

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  • D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease. International journal

    Satoko Umeda, Tomohisa Sujino, Kentaro Miyamoto, Yusuke Yoshimatsu, Yosuke Harada, Keita Nishiyama, Yoshimasa Aoto, Keika Adachi, Naoki Hayashi, Kimiko Amafuji, Nobuko Moritoki, Shinsuke Shibata, Nobuo Sasaki, Masashi Mita, Shun Tanemoto, Keiko Ono, Yohei Mikami, Jumpei Sasabe, Kaoru Takabayashi, Naoki Hosoe, Toshihiko Suzuki, Toshiro Sato, Koji Atarashi, Toshiaki Teratani, Haruhiko Ogata, Nobuhiro Nakamoto, Daisuke Shiomi, Hiroshi Ashida, Takanori Kanai

    Cellular and molecular gastroenterology and hepatology   16 ( 6 )   1011 - 1031   2023

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

    DOI： 10.1016/j.jcmgh.2023.08.002

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  • Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. International journal

    Yoshinaga Kawano, Madeline Edwards, Yiming Huang, Angelina M Bilate, Leandro P Araujo, Takeshi Tanoue, Koji Atarashi, Mark S Ladinsky, Steven L Reiner, Harris H Wang, Daniel Mucida, Kenya Honda, Ivaylo I Ivanov

    Cell   185 ( 19 )   3501 - 3519   2022.9

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    How intestinal microbes regulate metabolic syndrome is incompletely understood. We show that intestinal microbiota protects against development of obesity, metabolic syndrome, and pre-diabetic phenotypes by inducing commensal-specific Th17 cells. High-fat, high-sugar diet promoted metabolic disease by depleting Th17-inducing microbes, and recovery of commensal Th17 cells restored protection. Microbiota-induced Th17 cells afforded protection by regulating lipid absorption across intestinal epithelium in an IL-17-dependent manner. Diet-induced loss of protective Th17 cells was mediated by the presence of sugar. Eliminating sugar from high-fat diets protected mice from obesity and metabolic syndrome in a manner dependent on commensal-specific Th17 cells. Sugar and ILC3 promoted outgrowth of Faecalibaculum rodentium that displaced Th17-inducing microbiota. These results define dietary and microbiota factors posing risk for metabolic syndrome. They also define a microbiota-dependent mechanism for immuno-pathogenicity of dietary sugar and highlight an elaborate interaction between diet, microbiota, and intestinal immunity in regulation of metabolic disorders.

    DOI： 10.1016/j.cell.2022.08.005

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  • Identification of trypsin-degrading commensals in the large intestine. International journal

    Youxian Li, Eiichiro Watanabe, Yusuke Kawashima, Damian R Plichta, Zhujun Wang, Makoto Ujike, Qi Yan Ang, Runrun Wu, Munehiro Furuichi, Kozue Takeshita, Koji Yoshida, Keita Nishiyama, Sean M Kearney, Wataru Suda, Masahira Hattori, Satoshi Sasajima, Takahiro Matsunaga, Xiaoxi Zhang, Kazuto Watanabe, Jun Fujishiro, Jason M Norman, Bernat Olle, Shutoku Matsuyama, Ho Namkoong, Yoshifumi Uwamino, Makoto Ishii, Koichi Fukunaga, Naoki Hasegawa, Osamu Ohara, Ramnik J Xavier, Koji Atarashi, Kenya Honda

    Nature   609 ( 7927 )   582 - 589   2022.9

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    Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1-3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.

    DOI： 10.1038/s41586-022-05181-3

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  • Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. International journal

    Federici S, Kredo-Russo S, Valdés-Mas R, Kviatcovsky D, Weinstock E, Matiuhin Y, Silberberg Y, Atarashi K, Furuichi M, Oka A, Liu B, Fibelman M, Weiner IN, Khabra E, Cullin N, Ben-Yishai N, Inbar D, Ben-David H, Nicenboim J, Kowalsman N, Lieb W, Kario E, Cohen T, Geffen YF, Zelcbuch L, Cohen A, Rappo U, Gahali-Sass I, Golembo M, Lev V, Dori-Bachash M, Shapiro H, Moresi C, Cuevas-Sierra A, Mohapatra G, Kern L, Zheng D, Nobs SP, Suez J, Stettner N, Harmelin A, Zak N, Puttagunta S, Bassan M, Honda K, Sokol H, Bang C, Franke A, Schramm C, Maharshak N, Sartor RB, Sorek R, Elinav E

    Cell   185 ( 16 )   2879 - 2898.e24   2022.8   （ ISSN:0092-8674 ）

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    Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.
    Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.

    DOI： 10.1016/j.cell.2022.07.003

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  • A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model International journal

    Chia-Wen Lin, Dian E. Septyaningtrias, Hsu-Wen Chao, Mikiko Konda, Koji Atarashi, Kozue Takeshita, Kota Tamada, Jun Nomura, Yohei Sasagawa, Kaori Tanaka, Itoshi Nikaido, Kenya Honda, Thomas J. McHugh, Toru Takumi

    MOLECULAR PSYCHIATRY   27 ( 8 )   3343 - 3354   2022.5   （ ISSN:1359-4184 eISSN:1476-5578 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGERNATURE  

    Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism. It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development. Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain. We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes. Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.

    DOI： 10.1038/s41380-022-01566-y

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  • Microbiota and cancer development

    Kenya Honda, Takahiro Matsunaga, Takeshi Tanoue, Koji Atarashi, Yuko Sato

    CANCER SCIENCE   113   714 - 714   2022.2

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  • Microbiota and cancer development

    Kenya Honda, Takahiro Matsunaga, Takeshi Tanoue, Koji Atarashi, Yuko Sato

    CANCER SCIENCE   113   714 - 714   2022.2   （ ISSN:1347-9032 eISSN:1349-7006 ）

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    Language：English   Publisher：WILEY  

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  • Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. International journal

    Yuko Sato, Koji Atarashi, Damian R Plichta, Yasumichi Arai, Satoshi Sasajima, Sean M Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin N Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi Itoh, Kyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan R Littman, Michael A Fischbach, Yoshifumi Uwamino, Takashi Inoue, Akira Honda, Masahira Hattori, Tsuyoshi Murai, Ramnik J Xavier, Nobuyoshi Hirose, Kenya Honda

    Nature   599 ( 7885 )   458 - +   2021.7

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    DOI： 10.1038/s41586-021-03832-5

  • Low diversity of gut microbiota in the early phase of post-bone marrow transplantation increases the risk of chronic graft-versus-host disease

    Tatsuya Konishi, Shinsuke Kusakabe, Akihisa Hino, Kyoko Inamoto, Kota Yoshifuji, Yuko Kiridoshi, Kozue Takeshita, Satoshi Sasajima, Takashi Toya, Aiko Igarashi, Yuho Najima, Takeshi Kobayashi, Noriko Doki, Daisuke Motooka, Shota Nakamura, Masahiro Suyama, Wataru Suda, Atsushi Shiota, Koji Atarashi, Masahira Hattori, Kenya Honda, Takafumi Yokota, Kazuteru Ohashi, Hirohiko Shibayama, Kentaro Fukushima, Kazuhiko Kakihana

    Bone Marrow Transplantation   56 ( 7 )   1728 - 1731   2021.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41409-021-01249-2

  • Staphylococcus cohnii is a potentially biotherapeutic skin commensal alleviating skin inflammation. International journal

    Yoshihiro Ito, Takashi Sasaki, Youxian Li, Takeshi Tanoue, Yuki Sugiura, Ashwin N Skelly, Wataru Suda, Yusuke Kawashima, Nobuyuki Okahashi, Eiichiro Watanabe, Hiroto Horikawa, Aiko Shiohama, Rina Kurokawa, Eiryo Kawakami, Hachiro Iseki, Hiroshi Kawasaki, Yoichiro Iwakura, Atsushi Shiota, Liansheng Yu, Junzo Hisatsune, Haruhiko Koseki, Motoyuki Sugai, Makoto Arita, Osamu Ohara, Takeshi Matsui, Makoto Suematsu, Masahira Hattori, Koji Atarashi, Masayuki Amagai, Kenya Honda

    Cell reports   35 ( 4 )   109052 - 109052   2021.4

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    DOI： 10.1016/j.celrep.2021.109052

  • Low diversity of gut microbiota in the early phase of post-bone marrow transplantation increases the risk of chronic graft-versus-host disease. International journal

    Tatsuya Konishi, Shinsuke Kusakabe, Akihisa Hino, Kyoko Inamoto, Kota Yoshifuji, Yuko Kiridoshi, Kozue Takeshita, Satoshi Sasajima, Takashi Toya, Aiko Igarashi, Yuho Najima, Takeshi Kobayashi, Noriko Doki, Daisuke Motooka, Shota Nakamura, Masahiro Suyama, Wataru Suda, Atsushi Shiota, Koji Atarashi, Masahira Hattori, Kenya Honda, Takafumi Yokota, Kazuteru Ohashi, Hirohiko Shibayama, Kentaro Fukushima, Kazuhiko Kakihana

    Bone marrow transplantation   56 ( 7 )   1728 - 1731   2021.3

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    DOI： 10.1038/s41409-021-01249-2

  • Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians

    Kenya Honda, Yuko Sato, Koji Atarashi, Damian Plichta, Yasumichi Arai, Satoshi Sasajima, Sean Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi Itoh, Kyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan Littman, Michael Fischbach, Masahira Hattori, Tsuyoshi Murai, Ramnik Xavier, Nobuyoshi Hirose

    2020.12

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    DOI： 10.21203/rs.3.rs-115113/v1

  • Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation. International journal

    Kota Yoshifuji, Kyoko Inamoto, Yuko Kiridoshi, Kozue Takeshita, Satoshi Sasajima, Yukiko Shiraishi, Yuko Yamashita, Yuko Nisaka, Yukari Ogura, Rie Takeuchi, Takashi Toya, Aiko Igarashi, Yuho Najima, Noriko Doki, Takeshi Kobayashi, Kazuteru Ohashi, Wataru Suda, Koji Atarashi, Atsushi Shiota, Masahira Hattori, Kenya Honda, Kazuhiko Kakihana

    Blood advances   4 ( 19 )   4607 - 4617   2020.10

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    DOI： 10.1182/bloodadvances.2020002604

  • TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn's disease. Reviewed International journal

    Manabu Nagayama, Tomonori Yano, Koji Atarashi, Takeshi Tanoue, Mariko Sekiya, Yasutoshi Kobayashi, Hirotsugu Sakamoto, Kouichi Miura, Keijiro Sunada, Takaaki Kawaguchi, Satoru Morita, Kayoko Sugita, Seiko Narushima, Nicolas Barnich, Jun Isayama, Yuko Kiridooshi, Atsushi Shiota, Wataru Suda, Masahira Hattori, Hironori Yamamoto, Kenya Honda

    Gut microbes   12 ( 1 )   1 - 14   2020.7

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    DOI： 10.1080/19490976.2020.1788898

  • Association of Gut Microbiota with Spontaneous Autoimmune Uveitis Studied by Human Flora Reconstitution of Germ-free Mice

    Amy Zhang, Reiko Horai, Ryan S. Salvador, Colm O'hUigin, Jonathan Badger, Wuxing Yuan, Vishal Thovarai, Katsuko Sudo, Koji Atarashi, Kenya Honda, Rachel Caspi

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   61 ( 7 )   2020.6

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  • USE OF A TARGETED BACTERIOPHAGE COCKTAIL FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES

    Yulia Matiuhin, Eyal Weinstock, Efrat Khabra, Akihiko Oka, Bo Liu, Jeremy Herzog, Koji Atarashi, Munehiro Furuichi, Naomi Fliss Isakov, Morin Fibelman, Hava Ben David, Yael Silberberg, Hadar Reichman, Myriam Golembo, Sailaja Puttagunta, Harry Sokol, Nitsan Maharshak, Kenya Honda, R. Balfour Sartor, Naomi Zak

    GASTROENTEROLOGY   158 ( 6 )   S2 - S2   2020.5

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  • Association of gut microbiota with spontaneous autoimmune uveitis studied by human flora reconstitution of germ-free mice

    Amy Zhang, Reiko Horai, Ryan S. Salvador, Colm O'hUigin, Jonathan Badger, Wuxing Yuan, Vishal Thovarai, Katsuko Sudo, Koji Atarashi, Kenya Honda, Rachel R. Caspi

    JOURNAL OF IMMUNOLOGY   204 ( 1 )   2020.5

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    Language：English  

  • HUMAN-DERIVED CLOSTRIDIUM VE202 STRAINS REDUCE ENTEROBACTERIACEAE AND FUSOBACTERIA AND REVERSE EXPERIMENTAL COLITIS INDUCED BY HUMAN GUT MICROBIOTA

    Akihiko Oka, Yoshiyuki Mishima, Gerold Bongers, Andrew Baltus, Jeremy Herzog, Bo Liu, Toshifumi Ohkusa, Koji Atarashi, Kenya Honda, Lani San Mateo, Scott Plevy, R. Balfour Sartor

    GASTROENTEROLOGY   158 ( 6 )   S474 - S474   2020.5

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  • Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Reviewed International journal

    Elena Zagato, Chiara Pozzi, Alice Bertocchi, Tiziana Schioppa, Fabiana Saccheri, Silvia Guglietta, Bruno Fosso, Laura Melocchi, Giulia Nizzoli, Jacopo Troisi, Marinella Marzano, Bianca Oresta, Ilaria Spadoni, Koji Atarashi, Sara Carloni, Stefania Arioli, Giulia Fornasa, Francesco Asnicar, Nicola Segata, Simone Guglielmetti, Kenya Honda, Graziano Pesole, William Vermi, Giuseppe Penna, Maria Rescigno

    Nature microbiology   5 ( 3 )   511 - 524   2020.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41564-019-0649-5

  • HUMAN-DERIVED CLOSTRIDIUM VE202 STRAINS REDUCE ENTEROBACTERIACEAE AND FUSOBACTERIA AND REVERSE EXPERIMENTAL COLITIS INDUCED BY HUMAN GUT MICROBIOTA

    Akihiko Oka, Yoshiyuki Mishima, Gerold Bongers, Andrew Baltus, Bo Liu, Jeremy Herzog, Toshifumi Ohkusa, Koji Atarashi, Kenya Honda, Lani San Mateo, Scott Plevy, R. Balfour Sartor

    GASTROENTEROLOGY   158 ( 3 )   S59 - S60   2020.2

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    Language：English  

  • HUMAN-DERIVED CLOSTRIDIUM VE202 STRAINS REDUCE ENTEROBACTERIACEAE AND FUSOBACTERIA AND REVERSE EXPERIMENTAL COLITIS INDUCED BY HUMAN GUT MICROBIOTA

    Akihiko Oka, Yoshiyuki Mishima, Gerold Bongers, Andrew Baltus, Bo Liu, Jeremy Herzog, Toshifumi Ohkusa, Koji Atarashi, Kenya Honda, Lani San Mateo, Scott Plevy, R. Balfour Sartor

    INFLAMMATORY BOWEL DISEASES   26   S36 - S37   2020.1

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    Language：English  

    DOI： 10.1093/ibd/zaa010.094

  • Mutualistic skin bacteria protect against dermatitis via the induction of steroid biosynthesis pathways

    Ito Y, Sasaki T, Kawakami E, Suda W, Atarashi K, Amagai M, Honda K

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   139 ( 9 )   S272 - S272   2019.9

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    Language：Others  

    Mutualistic skin bacteria protect against dermatitis via the induction of steroid biosynthesis pathways

  • Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Reviewed International journal

    Nobuhiro Nakamoto, Nobuo Sasaki, Ryo Aoki, Kentaro Miyamoto, Wataru Suda, Toshiaki Teratani, Takahiro Suzuki, Yuzo Koda, Po-Sung Chu, Nobuhito Taniki, Akihiro Yamaguchi, Mitsuhiro Kanamori, Nobuhiko Kamada, Masahira Hattori, Hiroshi Ashida, Michiie Sakamoto, Koji Atarashi, Seiko Narushima, Akihiko Yoshimura, Kenya Honda, Toshiro Sato, Takanori Kanai

    Nature microbiology   4 ( 3 )   492 - 503   2019.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41564-018-0333-1

  • IL-10 produced by macrophages regulates epithelial integrity in the small intestine. Reviewed International journal

    Scientific reports   9 ( 1 )   1223 - 1223   2019.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41598-018-38125-x

  • A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Reviewed International journal

    Takeshi Tanoue, Satoru Morita, Damian R Plichta, Ashwin N Skelly, Wataru Suda, Yuki Sugiura, Seiko Narushima, Hera Vlamakis, Iori Motoo, Kayoko Sugita, Atsushi Shiota, Kozue Takeshita, Keiko Yasuma-Mitobe, Dieter Riethmacher, Tsuneyasu Kaisho, Jason M Norman, Daniel Mucida, Makoto Suematsu, Tomonori Yaguchi, Vanni Bucci, Takashi Inoue, Yutaka Kawakami, Bernat Olle, Bruce Roberts, Masahira Hattori, Ramnik J Xavier, Koji Atarashi, Kenya Honda

    Nature   565 ( 7741 )   600 - 605   2019.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41586-019-0878-z

  • Commensal bacteria that can induce CD8 T cells and cancer immunity

    Takeshi Tanoue, Koji Atarashi, Kenya Honda

    CANCER SCIENCE   109   348 - 348   2018.12

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  • IL-10-INDEPENDENT PROTECTIVE ACTIVITIES OF HUMAN-DERIVED CLOSTRIDIUM STRAINS IN EXPERIMENTAL COLITIS

    Akihiko Oka, Yoshiyuki Mishima, Gerold Bongers, Bo Liu, Jeremy Herzog, Andrew Baltus, Debbie Marshall, Matthias Hesse, Koji Atarashi, Shinji Fukuda, Kenya Honda, Lani San Mateo, Scott Plevy, R. Balfour Sartor

    GASTROENTEROLOGY   154 ( 6 )   S1036 - S1036   2018.5

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    Language：English  

  • Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia. Reviewed International journal

    Ho Namkoong, Makoto Ishii, Hideki Fujii, Kazuma Yagi, Takahiro Asami, Takanori Asakura, Shoji Suzuki, Ahmed E Hegab, Hirofumi Kamata, Sadatomo Tasaka, Koji Atarashi, Nobuhiro Nakamoto, Satoshi Iwata, Kenya Honda, Takanori Kanai, Naoki Hasegawa, Shigeo Koyasu, Tomoko Betsuyaku

    PLoS pathogens   14 ( 4 )   e1006955   2018.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.ppat.1006955

  • The gut microbiota and cancer immunity

    Kenya Honda, Takeshi Tanoue, Koji Atarashi

    CANCER SCIENCE   109   153 - 153   2018.1

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    Language：English  

  • Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Reviewed International journal

    Koji Atarashi, Wataru Suda, Chengwei Luo, Takaaki Kawaguchi, Iori Motoo, Seiko Narushima, Yuya Kiguchi, Keiko Yasuma, Eiichiro Watanabe, Takeshi Tanoue, Christoph A Thaiss, Mayuko Sato, Kiminori Toyooka, Heba S Said, Hirokazu Yamagami, Scott A Rice, Dirk Gevers, Ryan C Johnson, Julia A Segre, Kong Chen, Jay K Kolls, Eran Elinav, Hidetoshi Morita, Ramnik J Xavier, Masahira Hattori, Kenya Honda

    Science (New York, N.Y.)   358 ( 6361 )   359 - 365   2017.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/science.aan4526

  • Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Reviewed International journal

    Koji Atarashi, Wataru Suda, Chengwei Luo, Takaaki Kawaguchi, Iori Motoo, Seiko Narushima, Yuya Kiguchi, Keiko Yasuma, Eiichiro Watanabe, Takeshi Tanoue, Christoph A Thaiss, Mayuko Sato, Kiminori Toyooka, Heba S Said, Hirokazu Yamagami, Scott A Rice, Dirk Gevers, Ryan C Johnson, Julia A Segre, Kong Chen, Jay K Kolls, Eran Elinav, Hidetoshi Morita, Ramnik J Xavier, Masahira Hattori, Kenya Honda

    Science (New York, N.Y.)   358 ( 6361 )   359 - 365   2017.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/science.aan4526

  • Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Reviewed International journal

    Sangdoo Kim, Hyunju Kim, Yeong Shin Yim, Soyoung Ha, Koji Atarashi, Tze Guan Tan, Randy S Longman, Kenya Honda, Dan R Littman, Gloria B Choi, Jun R Huh

    Nature   549 ( 7673 )   528 - 532   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature23910

  • Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. Reviewed International journal

    Noriko Doki, Masahiro Suyama, Satoshi Sasajima, Junko Ota, Aiko Igarashi, Iyo Mimura, Hidetoshi Morita, Yuki Fujioka, Daisuke Sugiyama, Hiroyoshi Nishikawa, Yutaka Shimazu, Wataru Suda, Kozue Takeshita, Koji Atarashi, Masahira Hattori, Eiichi Sato, Kyoko Watakabe-Inamoto, Kosuke Yoshioka, Yuho Najima, Takeshi Kobayashi, Kazuhiko Kakihana, Naoto Takahashi, Hisashi Sakamaki, Kenya Honda, Kazuteru Ohashi

    Annals of hematology   96 ( 9 )   1517 - 1523   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s00277-017-3069-8

  • Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Reviewed International journal

    Sangdoo Kim, Hyunju Kim, Yeong Shin Yim, Soyoung Ha, Koji Atarashi, Tze Guan Tan, Randy S Longman, Kenya Honda, Dan R Littman, Gloria B Choi, Jun R Huh

    Nature   549 ( 7673 )   528 - 532   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature23910

  • Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. Reviewed International journal

    Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata

    Journal of lipid research   58 ( 3 )   519 - 528   2017.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1194/jlr.M072165

  • Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. Reviewed International journal

    Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata

    Journal of lipid research   58 ( 3 )   519 - 528   2017.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1194/jlr.M072165

  • Corrigendum: A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Reviewed International journal

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J Lafaille, Maria A Curotto de Lafaille

    Scientific reports   6   34899 - 34899   2016.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep34899

  • A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers (vol 6, 30784, 2016)

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G. Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H. Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J. Lafaille, Maria A. Curotto de Lafaille

    SCIENTIFIC REPORTS   6   519 - 528   2016.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep34899

  • Corrigendum: A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Reviewed International journal

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J Lafaille, Maria A Curotto de Lafaille

    Scientific reports   6   34899 - 34899   2016.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep34899

  • A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers (vol 6, 30784, 2016)

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G. Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H. Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J. Lafaille, Maria A. Curotto de Lafaille

    SCIENTIFIC REPORTS   6   519 - 528   2016.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep34899

  • A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Reviewed International journal

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J Lafaille, Maria A Curotto de Lafaille

    Scientific reports   6   30784 - 30784   2016.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep30784

  • A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. Reviewed International journal

    Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J Lafaille, Maria A Curotto de Lafaille

    Scientific reports   6   30784 - 30784   2016.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep30784

  • Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers

    Takuro Saito, Hiroyoshi Nishikawa, Hisashi Wada, Yuji Nagano, Daisuke Sugiyama, Koji Atarashi, Yuka Maeda, Masahide Hamaguchi, Naganari Ohkura, Eiichi Sato, Hirotsugu Nagase, Junichi Nishimura, Hirofumi Yamamoto, Shuji Takiguchi, Takeshi Tanoue, Wataru Suda, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Masaki Mori, Yuichiro Doki, Shimon Sakaguchi

    NATURE MEDICINE   22 ( 6 )   679 - +   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nm.4086

  • Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine. Reviewed International journal

    Takanori Ochi, Yongjia Feng, Sho Kitamoto, Hiroko Nagao-Kitamoto, Peter Kuffa, Koji Atarashi, Kenya Honda, Daniel H Teitelbaum, Nobuhiko Kamada

    Scientific reports   6   27634 - 27634   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep27634

  • Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Reviewed International journal

    Takuro Saito, Hiroyoshi Nishikawa, Hisashi Wada, Yuji Nagano, Daisuke Sugiyama, Koji Atarashi, Yuka Maeda, Masahide Hamaguchi, Naganari Ohkura, Eiichi Sato, Hirotsugu Nagase, Junichi Nishimura, Hirofumi Yamamoto, Shuji Takiguchi, Takeshi Tanoue, Wataru Suda, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Masaki Mori, Yuichiro Doki, Shimon Sakaguchi

    Nature medicine   22 ( 6 )   679 - 84   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nm.4086

  • Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers

    Takuro Saito, Hiroyoshi Nishikawa, Hisashi Wada, Yuji Nagano, Daisuke Sugiyama, Koji Atarashi, Yuka Maeda, Masahide Hamaguchi, Naganari Ohkura, Eiichi Sato, Hirotsugu Nagase, Junichi Nishimura, Hirofumi Yamamoto, Shuji Takiguchi, Takeshi Tanoue, Wataru Suda, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Masaki Mori, Yuichiro Doki, Shimon Sakaguchi

    NATURE MEDICINE   22 ( 6 )   679 - +   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nm.4086

  • Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine. Reviewed International journal

    Takanori Ochi, Yongjia Feng, Sho Kitamoto, Hiroko Nagao-Kitamoto, Peter Kuffa, Koji Atarashi, Kenya Honda, Daniel H Teitelbaum, Nobuhiko Kamada

    Scientific reports   6   27634 - 27634   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep27634

  • Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Reviewed International journal

    Takuro Saito, Hiroyoshi Nishikawa, Hisashi Wada, Yuji Nagano, Daisuke Sugiyama, Koji Atarashi, Yuka Maeda, Masahide Hamaguchi, Naganari Ohkura, Eiichi Sato, Hirotsugu Nagase, Junichi Nishimura, Hirofumi Yamamoto, Shuji Takiguchi, Takeshi Tanoue, Wataru Suda, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Masaki Mori, Yuichiro Doki, Shimon Sakaguchi

    Nature medicine   22 ( 6 )   679 - 84   2016.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nm.4086

  • Development and maintenance of intestinal regulatory T cells. Reviewed International journal

    Takeshi Tanoue, Koji Atarashi, Kenya Honda

    Nature reviews. Immunology   16 ( 5 )   295 - 309   2016.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nri.2016.36

  • Development and maintenance of intestinal regulatory T cells. Reviewed International journal

    Takeshi Tanoue, Koji Atarashi, Kenya Honda

    Nature reviews. Immunology   16 ( 5 )   295 - 309   2016.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nri.2016.36

  • Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Reviewed International journal

    Cell   163 ( 2 )   367 - 80   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.cell.2015.08.058

  • Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis. Reviewed International journal

    Junko Nishio, Minato Baba, Koji Atarashi, Takeshi Tanoue, Hideo Negishi, Hideyuki Yanai, Sonoko Habu, Shohei Hori, Kenya Honda, Tadatsugu Taniguchi

    Proceedings of the National Academy of Sciences of the United States of America   112 ( 41 )   12770 - 5   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.1516617112

  • Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Reviewed International journal

    Cell   163 ( 2 )   367 - 80   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.cell.2015.08.058

  • Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis. Reviewed International journal

    Junko Nishio, Minato Baba, Koji Atarashi, Takeshi Tanoue, Hideo Negishi, Hideyuki Yanai, Sonoko Habu, Shohei Hori, Kenya Honda, Tadatsugu Taniguchi

    Proceedings of the National Academy of Sciences of the United States of America   112 ( 41 )   12770 - 5   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.1516617112

  • The microbiota regulates type 2 immunity through RORγt+ T cells Reviewed International journal

    Ohnmacht Caspar, Park Joo Hong, Cording Sascha, Wing James B, Atarashi Koji, Obata Yuuki, Gaboriau-Routhiau Valérie, Marques Rute, Dulauroy Sophie, Fedoseeva Maria, Busslinger Meinrad, Cerf-Bensussan Nadine, Boneca Ivo G, Voehringer David, Hase Koji, Honda Kenya, Sakaguchi Shimon, Eberl Gérard

    349 ( 6251 )   989 - 93   2015.8

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    <p>Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T<inf>H</inf>17) cells and regulatory T cells (T<inf>regs</inf>) in the intestine. Here, we report that microbiota-induced T<inf>regs</inf> express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to T<inf>H</inf>17 cells. In the absence of RORγt+ T<inf>regs</inf>, T<inf>H</inf>2-driven defense against helminths is more efficient, whereas T<inf>H</inf>2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ T<inf>regs</inf> and T<inf>H</inf>17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.</p>

    DOI： 10.1126/science.aac4263

  • The microbiota regulates type 2 immunity through RORγt+ T cells Reviewed International journal

    Ohnmacht Caspar, Park Joo Hong, Cording Sascha, Wing James B, Atarashi Koji, Obata Yuuki, Gaboriau-Routhiau Valérie, Marques Rute, Dulauroy Sophie, Fedoseeva Maria, Busslinger Meinrad, Cerf-Bensussan Nadine, Boneca Ivo G, Voehringer David, Hase Koji, Honda Kenya, Sakaguchi Shimon, Eberl Gérard

    349 ( 6251 )   989 - 93   2015.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T<inf>H</inf>17) cells and regulatory T cells (T<inf>regs</inf>) in the intestine. Here, we report that microbiota-induced T<inf>regs</inf> express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to T<inf>H</inf>17 cells. In the absence of RORγt+ T<inf>regs</inf>, T<inf>H</inf>2-driven defense against helminths is more efficient, whereas T<inf>H</inf>2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ T<inf>regs</inf> and T<inf>H</inf>17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.</p>

    DOI： 10.1126/science.aac4263

  • Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Reviewed International journal

    Shimpei Kawamoto, Mikako Maruya, Lucia M Kato, Wataru Suda, Koji Atarashi, Yasuko Doi, Yumi Tsutsui, Hongyan Qin, Kenya Honda, Takaharu Okada, Masahira Hattori, Sidonia Fagarasan

    Immunity   41 ( 1 )   152 - 65   2014.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2014.05.016

  • Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Reviewed International journal

    Shimpei Kawamoto, Mikako Maruya, Lucia M Kato, Wataru Suda, Koji Atarashi, Yasuko Doi, Yumi Tsutsui, Hongyan Qin, Kenya Honda, Takaharu Okada, Masahira Hattori, Sidonia Fagarasan

    Immunity   41 ( 1 )   152 - 65   2014.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2014.05.016

  • The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. Reviewed International journal

    Yuuki Obata, Yukihiro Furusawa, Takaho A Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I Kawamura, Taeko Dohi, Shoji Tajima, Hiroshi Masumoto, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki, Koji Hase

    Nature immunology   15 ( 6 )   571 - 9   2014.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2886

  • The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. Reviewed International journal

    Yuuki Obata, Yukihiro Furusawa, Takaho A Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I Kawamura, Taeko Dohi, Shoji Tajima, Hiroshi Masumoto, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki, Koji Hase

    Nature immunology   15 ( 6 )   571 - 9   2014.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2886

  • The epigenetic regulator Uhrf1 is critical for functional expansion of colonic regulatory T cells. Reviewed

    Obata Y, Furusawa Y, Endo TA, Sharif J, Takahashi D, Atarashi K, Onawa S, Fujimura Y, Takahashi M, Ikawa T, Otsubo T, Kawamura YI, Dohi T, Tajima S, Ohara O, Honda K, Hori S, Ohno H, Koseki H, Hase K

    Nat Immunol   15   571-579   2014.5

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    Epigenetic regulator Uhrf1 is critical for functional expansion of colonic regulatory T cells.

  • Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia

    Narushima Seiko, Sugiura Yuki, Oshima Kenshiro, Atarashi Koji, Hattori Masahira, Suematsu Makoto, Honda Kenya

    Gut Microbes   5 ( 3 )   333 - 339   2014.5

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    Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia
    <p>The gut microbiota plays important roles in the development of the host immune system. We have previously shown that a combination of 46 strains of commensal Clostridia isolated from conventionally reared mice can induce the accumulation of CD4(+)Foxp3(+) regulatory T (Treg) cells in the mouse colonic lamina propria. Subsequently, we succeeded in isolating and selecting 17 strains of Clostridia from a healthy human fecal sample that can significantly increase the number and function of colonic Treg cells in colonized rodents, thereby attenuating symptoms of experimental allergic diarrhea and colitis. Here we characterize each of the 17 strains of human-derived Clostridia in terms of sensitivity to antibiotics and ability to produce short chain fatty acids and other metabolites, and discuss their potential as biotherapeutics to correct dysbiosis and treat immune-inflammatory diseases. </p>

    DOI： 10.4161/gmic.28572

  • The epigenetic regulator Uhrf1 is critical for functional expansion of colonic regulatory T cells. Reviewed

    Obata Y, Furusawa Y, Endo TA, Sharif J, Takahashi D, Atarashi K, Onawa S, Fujimura Y, Takahashi M, Ikawa T, Otsubo T, Kawamura YI, Dohi T, Tajima S, Ohara O, Honda K, Hori S, Ohno H, Koseki H, Hase K

    Nat Immunol   15   571-579   2014.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    Epigenetic regulator Uhrf1 is critical for functional expansion of colonic regulatory T cells.

  • Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia

    Narushima Seiko, Sugiura Yuki, Oshima Kenshiro, Atarashi Koji, Hattori Masahira, Suematsu Makoto, Honda Kenya

    Gut Microbes   5 ( 3 )   333 - 339   2014.5

    　More details

    Language：English   Publishing type：Research paper (scientific journal)  

    Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia
    <p>The gut microbiota plays important roles in the development of the host immune system. We have previously shown that a combination of 46 strains of commensal Clostridia isolated from conventionally reared mice can induce the accumulation of CD4(+)Foxp3(+) regulatory T (Treg) cells in the mouse colonic lamina propria. Subsequently, we succeeded in isolating and selecting 17 strains of Clostridia from a healthy human fecal sample that can significantly increase the number and function of colonic Treg cells in colonized rodents, thereby attenuating symptoms of experimental allergic diarrhea and colitis. Here we characterize each of the 17 strains of human-derived Clostridia in terms of sensitivity to antibiotics and ability to produce short chain fatty acids and other metabolites, and discuss their potential as biotherapeutics to correct dysbiosis and treat immune-inflammatory diseases. </p>

    DOI： 10.4161/gmic.28572

  • MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells Reviewed International journal

    57 ( 2 )   100 - 10   2014.2

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    <p>Measles virus (MV) infects CD150Tg/Ifnar (IFN alpha receptor)-/- mice but not CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow-derived dendritic cells (BMDCs) from CD150Tg/Ifnar-/- mice are permissive to MV in contrast to those from simple CD150Tg mice, which reveals a crucial role of type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA virus infection usually allows cells to generate double-stranded RNA and induce activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to the production of type I IFN through the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found CD150Tg/Mavs-/-BMDCs, but not CD150Tg/Irf3-/-/Irf7-/-BMDCs, permissive to MV. IFN-α/β were not induced in MV-infected CD150Tg/Mavs-/-BMDCs, while IFN-β was subtly induced in CD150Tg/Irf3-/-/Irf7-/-BMDCs. In vivo systemic infection was

    DOI： 10.1016/j.molimm.2013.08.007

  • Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells (vol 504, pg 446, 2013)

    Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N. Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M. Clarke, David L. Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, Jun Kikuchi, Kenya Honda, Koji Hase, Hiroshi Ohno

    NATURE   506 ( 7487 )   2014.2

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    Language：English  

    DOI： 10.1038/nature13041

  • MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells Reviewed International journal

    57 ( 2 )   100 - 10   2014.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Measles virus (MV) infects CD150Tg/Ifnar (IFN alpha receptor)-/- mice but not CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow-derived dendritic cells (BMDCs) from CD150Tg/Ifnar-/- mice are permissive to MV in contrast to those from simple CD150Tg mice, which reveals a crucial role of type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA virus infection usually allows cells to generate double-stranded RNA and induce activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to the production of type I IFN through the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found CD150Tg/Mavs-/-BMDCs, but not CD150Tg/Irf3-/-/Irf7-/-BMDCs, permissive to MV. IFN-α/β were not induced in MV-infected CD150Tg/Mavs-/-BMDCs, while IFN-β was subtly induced in CD150Tg/Irf3-/-/Irf7-/-BMDCs. In vivo systemic infection was

    DOI： 10.1016/j.molimm.2013.08.007

  • Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells (vol 504, pg 446, 2013)

    Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N. Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M. Clarke, David L. Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, Jun Kikuchi, Kenya Honda, Koji Hase, Hiroshi Ohno

    NATURE   506 ( 7487 )   2014.2

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    Language：English  

    DOI： 10.1038/nature13041

  • Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Reviewed International journal

    Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M Clarke, David L Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, Jun Kikuchi, Kenya Honda, Koji Hase, Hiroshi Ohno

    Nature   504 ( 7480 )   446 - 50   2013.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12721

  • Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Reviewed International journal

    Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M Clarke, David L Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, Jun Kikuchi, Kenya Honda, Koji Hase, Hiroshi Ohno

    Nature   504 ( 7480 )   446 - 50   2013.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12721

  • Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. Reviewed International journal

    Immunity   39 ( 3 )   584 - 98   2013.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2013.06.019

  • Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses

    Hideaki Ohyagi, Nobuyuki Onai, Taku Sato, Satoshi Yotsumoto, Jiajia Liu, Hisaya Akiba, Hideo Yagita, Koji Atarashi, Kenya Honda, Axel Roers, Werner Mueller, Kazutaka Kurabayashi, Mayuka Hosoi-Amaike, Naoto Takahashi, Makoto Hirokawa, Kouji Matsushima, Kenichi Sawada, Toshiaki Ohteki

    IMMUNITY   39 ( 3 )   584 - 598   2013.9

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    DOI： 10.1016/j.immuni.2013.06.019

  • Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. Reviewed International journal

    Immunity   39 ( 3 )   584 - 98   2013.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2013.06.019

  • Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses

    Hideaki Ohyagi, Nobuyuki Onai, Taku Sato, Satoshi Yotsumoto, Jiajia Liu, Hisaya Akiba, Hideo Yagita, Koji Atarashi, Kenya Honda, Axel Roers, Werner Mueller, Kazutaka Kurabayashi, Mayuka Hosoi-Amaike, Naoto Takahashi, Makoto Hirokawa, Kouji Matsushima, Kenichi Sawada, Toshiaki Ohteki

    IMMUNITY   39 ( 3 )   584 - 598   2013.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2013.06.019

  • Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Reviewed International journal

    Nature   500 ( 7461 )   232 - 6   2013.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12331

  • Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Reviewed International journal

    Nature   500 ( 7461 )   232 - 6   2013.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12331

  • Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Reviewed International journal

    Shin Yoshimoto, Tze Mun Loo, Koji Atarashi, Hiroaki Kanda, Seidai Sato, Seiichi Oyadomari, Yoichiro Iwakura, Kenshiro Oshima, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Yuichi Ishikawa, Eiji Hara, Naoko Ohtani

    Nature   499 ( 7456 )   97 - 101   2013.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12347

  • Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Reviewed International journal

    Shin Yoshimoto, Tze Mun Loo, Koji Atarashi, Hiroaki Kanda, Seidai Sato, Seiichi Oyadomari, Yoichiro Iwakura, Kenshiro Oshima, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Yuichi Ishikawa, Eiji Hara, Naoko Ohtani

    Nature   499 ( 7456 )   97 - 101   2013.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature12347

  • IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Reviewed International journal

    Andreas Schlitzer, Naomi McGovern, Pearline Teo, Teresa Zelante, Koji Atarashi, Donovan Low, Adrian W S Ho, Peter See, Amanda Shin, Pavandip Singh Wasan, Guillaume Hoeffel, Benoit Malleret, Alexander Heiseke, Samantha Chew, Laura Jardine, Harriet A Purvis, Catharien M U Hilkens, John Tam, Michael Poidinger, E Richard Stanley, Anne B Krug, Laurent Renia, Baalasubramanian Sivasankar, Lai Guan Ng, Matthew Collin, Paola Ricciardi-Castagnoli, Kenya Honda, Muzlifah Haniffa, Florent Ginhoux

    Immunity   38 ( 5 )   970 - 83   2013.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2013.04.011

  • IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Reviewed International journal

    Andreas Schlitzer, Naomi McGovern, Pearline Teo, Teresa Zelante, Koji Atarashi, Donovan Low, Adrian W S Ho, Peter See, Amanda Shin, Pavandip Singh Wasan, Guillaume Hoeffel, Benoit Malleret, Alexander Heiseke, Samantha Chew, Laura Jardine, Harriet A Purvis, Catharien M U Hilkens, John Tam, Michael Poidinger, E Richard Stanley, Anne B Krug, Laurent Renia, Baalasubramanian Sivasankar, Lai Guan Ng, Matthew Collin, Paola Ricciardi-Castagnoli, Kenya Honda, Muzlifah Haniffa, Florent Ginhoux

    Immunity   38 ( 5 )   970 - 83   2013.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2013.04.011

  • Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes. Reviewed International journal

    14 ( 3 )   281 - 9   2013.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    TCRαβ thymocytes differentiate into either CD8αβ(+) cytotoxic T lymphocytes or CD4(+) helper T cells. This functional dichotomy is controlled by key transcription factors, including the helper T cell master regulator ThPOK, which suppresses the cytolytic program in major histocompatibility complex (MHC) class II-restricted CD4(+) thymocytes. ThPOK continues to repress genes of the CD8 lineage in mature CD4(+) T cells, even as they differentiate into effector helper T cell subsets. Here we found that the helper T cell fate was not fixed and that mature, antigen-stimulated CD4(+) T cells terminated expression of the gene encoding ThPOK and reactivated genes of the CD8 lineage. This unexpected plasticity resulted in the post-thymic termination of the helper T cell program and the functional differentiation of distinct MHC class II-restricted CD4(+) cytotoxic T lymphocytes.

    DOI： 10.1038/ni.2523

  • Transcriptional reprogramming of mature CD4(+) helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes

    Daniel Mucida, Mohammad Mushtaq Husain, Sawako Muroi, Femke van Wijk, Ryo Shinnakasu, Yoshinori Naoe, Bernardo Sgarbi Reis, Yujun Huang, Florence Lambolez, Michael Docherty, Antoine Attinger, Jr-Wen Shui, Gisen Kim, Christopher J. Lena, Shinya Sakaguchi, Chizuko Miyamoto, Peng Wang, Koji Atarashi, Yunji Park, Toshinori Nakayama, Kenya Honda, Wilfried Ellmeier, Mitchell Kronenberg, Ichiro Taniuchi, Hilde Cheroutre

    NATURE IMMUNOLOGY   14 ( 3 )   281 - 289   2013.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2523

  • Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes. Reviewed International journal

    14 ( 3 )   281 - 9   2013.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    TCRαβ thymocytes differentiate into either CD8αβ(+) cytotoxic T lymphocytes or CD4(+) helper T cells. This functional dichotomy is controlled by key transcription factors, including the helper T cell master regulator ThPOK, which suppresses the cytolytic program in major histocompatibility complex (MHC) class II-restricted CD4(+) thymocytes. ThPOK continues to repress genes of the CD8 lineage in mature CD4(+) T cells, even as they differentiate into effector helper T cell subsets. Here we found that the helper T cell fate was not fixed and that mature, antigen-stimulated CD4(+) T cells terminated expression of the gene encoding ThPOK and reactivated genes of the CD8 lineage. This unexpected plasticity resulted in the post-thymic termination of the helper T cell program and the functional differentiation of distinct MHC class II-restricted CD4(+) cytotoxic T lymphocytes.

    DOI： 10.1038/ni.2523

  • Transcriptional reprogramming of mature CD4(+) helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes

    Daniel Mucida, Mohammad Mushtaq Husain, Sawako Muroi, Femke van Wijk, Ryo Shinnakasu, Yoshinori Naoe, Bernardo Sgarbi Reis, Yujun Huang, Florence Lambolez, Michael Docherty, Antoine Attinger, Jr-Wen Shui, Gisen Kim, Christopher J. Lena, Shinya Sakaguchi, Chizuko Miyamoto, Peng Wang, Koji Atarashi, Yunji Park, Toshinori Nakayama, Kenya Honda, Wilfried Ellmeier, Mitchell Kronenberg, Ichiro Taniuchi, Hilde Cheroutre

    NATURE IMMUNOLOGY   14 ( 3 )   281 - 289   2013.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2523

  • Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. Reviewed International journal

    Takashi Kusu, Hisako Kayama, Makoto Kinoshita, Seong Gyu Jeon, Yoshiyasu Ueda, Yoshiyuki Goto, Ryu Okumura, Hiroyuki Saiga, Takashi Kurakawa, Kayo Ikeda, Yuichi Maeda, Jun-ichi Nishimura, Yasunobu Arima, Koji Atarashi, Kenya Honda, Masaaki Murakami, Jun Kunisawa, Hiroshi Kiyono, Meinoshin Okumura, Masahiro Yamamoto, Kiyoshi Takeda

    Journal of immunology (Baltimore, Md. : 1950)   190 ( 2 )   774 - 83   2013.1

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    DOI： 10.4049/jimmunol.1103067

  • Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. Reviewed International journal

    Takashi Kusu, Hisako Kayama, Makoto Kinoshita, Seong Gyu Jeon, Yoshiyasu Ueda, Yoshiyuki Goto, Ryu Okumura, Hiroyuki Saiga, Takashi Kurakawa, Kayo Ikeda, Yuichi Maeda, Jun-ichi Nishimura, Yasunobu Arima, Koji Atarashi, Kenya Honda, Masaaki Murakami, Jun Kunisawa, Hiroshi Kiyono, Meinoshin Okumura, Masahiro Yamamoto, Kiyoshi Takeda

    Journal of immunology (Baltimore, Md. : 1950)   190 ( 2 )   774 - 83   2013.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.4049/jimmunol.1103067

  • Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Reviewed International journal

    Hideo Negishi, Hideyuki Yanai, Akira Nakajima, Ryuji Koshiba, Koji Atarashi, Atsushi Matsuda, Kosuke Matsuki, Shoji Miki, Takahiro Doi, Alan Aderem, Junko Nishio, Stephen T Smale, Kenya Honda, Tadatsugu Taniguchi

    Nature immunology   13 ( 7 )   659 - 66   2012.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2307

  • Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Reviewed International journal

    Hideo Negishi, Hideyuki Yanai, Akira Nakajima, Ryuji Koshiba, Koji Atarashi, Atsushi Matsuda, Kosuke Matsuki, Shoji Miki, Takahiro Doi, Alan Aderem, Junko Nishio, Stephen T Smale, Kenya Honda, Tadatsugu Taniguchi

    Nature immunology   13 ( 7 )   659 - 66   2012.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2307

  • Microbial recognition and pathogen-associated molecular pattern receptors in inflammatory bowel disease Reviewed

    Kenya Honda, Koji Atarashi, Junko Nishio

    Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach   97 - 110   2012.1

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    Language：English  

    DOI： 10.1007/978-1-4614-0998-4_6

  • Microbial recognition and pathogen-associated molecular pattern receptors in inflammatory bowel disease Reviewed

    Kenya Honda, Koji Atarashi, Junko Nishio

    Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach   97 - 110   2012.1

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    Language：English  

    DOI： 10.1007/978-1-4614-0998-4_6

  • Microbiota in autoimmunity and tolerance. Reviewed International journal

    Koji Atarashi, Kenya Honda

    Current opinion in immunology   23 ( 6 )   761 - 8   2011.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.coi.2011.11.002

  • Microbiota in autoimmunity and tolerance. Reviewed International journal

    Koji Atarashi, Kenya Honda

    Current opinion in immunology   23 ( 6 )   761 - 8   2011.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.coi.2011.11.002

  • The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Reviewed International journal

    Yasutaka Motomura, Hiroshi Kitamura, Atsushi Hijikata, Yuko Matsunaga, Koichiro Matsumoto, Hiromasa Inoue, Koji Atarashi, Shohei Hori, Hiroshi Watarai, Jinfang Zhu, Masaru Taniguchi, Masato Kubo

    Nature immunology   12 ( 5 )   450 - 9   2011.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2020

  • The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Reviewed International journal

    Yasutaka Motomura, Hiroshi Kitamura, Atsushi Hijikata, Yuko Matsunaga, Koichiro Matsumoto, Hiromasa Inoue, Koji Atarashi, Shohei Hori, Hiroshi Watarai, Jinfang Zhu, Masaru Taniguchi, Masato Kubo

    Nature immunology   12 ( 5 )   450 - 9   2011.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ni.2020

  • Microbiotal influence on T cell subset development. Reviewed International journal

    Koji Atarashi, Yoshinori Umesaki, Kenya Honda

    Seminars in immunology   23 ( 2 )   146 - 53   2011.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.smim.2011.01.010

  • Microbiotal influence on T cell subset development. Reviewed International journal

    Koji Atarashi, Yoshinori Umesaki, Kenya Honda

    Seminars in immunology   23 ( 2 )   146 - 53   2011.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.smim.2011.01.010

  • Induction of colonic regulatory T cells by indigenous Clostridium species. Reviewed International journal

    Koji Atarashi, Takeshi Tanoue, Tatsuichiro Shima, Akemi Imaoka, Tomomi Kuwahara, Yoshika Momose, Genhong Cheng, Sho Yamasaki, Takashi Saito, Yusuke Ohba, Tadatsugu Taniguchi, Kiyoshi Takeda, Shohei Hori, Ivaylo I Ivanov, Yoshinori Umesaki, Kikuji Itoh, Kenya Honda

    Science (New York, N.Y.)   331 ( 6015 )   337 - 41   2011.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/science.1198469

  • Induction of colonic regulatory T cells by indigenous Clostridium species. Reviewed International journal

    Koji Atarashi, Takeshi Tanoue, Tatsuichiro Shima, Akemi Imaoka, Tomomi Kuwahara, Yoshika Momose, Genhong Cheng, Sho Yamasaki, Takashi Saito, Yusuke Ohba, Tadatsugu Taniguchi, Kiyoshi Takeda, Shohei Hori, Ivaylo I Ivanov, Yoshinori Umesaki, Kikuji Itoh, Kenya Honda

    Science (New York, N.Y.)   331 ( 6015 )   337 - 41   2011.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/science.1198469

  • Regulation of Th17 cell differentiation by intestinal commensal bacteria

    K. Atarashi, T. Tanoue, Y. Umesaki, K. Honda

    BENEFICIAL MICROBES   1 ( 4 )   327 - 334   2010.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3920/BM2010.0026

  • Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

    Atarashi Koji, Tanoue Takeshi, Shima Tatsuichiro, Imaoka Akemi, Kuwahara Tomomi, Momose Yoshika, Cheng Genhong, Yamasaki Sho, Saito Takashi, Ohba Yusuke, Taniguchi Tadatsugu, Takeda Kiyoshi, Hori Shohei, Ivanov Ivaylo I, Umesaki Yoshinori, Itoh Kikuji, Honda Kenya

    Science   1 - 5   2010.12

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    Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
    <p>CD4+ T regulatory cells (Tregs), expressing the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota-particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-β (TGF-β) and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic IgE responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.</p>

    DOI： 10.1126/science.

  • Regulation of Th17 cell differentiation by intestinal commensal bacteria

    K. Atarashi, T. Tanoue, Y. Umesaki, K. Honda

    BENEFICIAL MICROBES   1 ( 4 )   327 - 334   2010.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3920/BM2010.0026

  • Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

    Atarashi Koji, Tanoue Takeshi, Shima Tatsuichiro, Imaoka Akemi, Kuwahara Tomomi, Momose Yoshika, Cheng Genhong, Yamasaki Sho, Saito Takashi, Ohba Yusuke, Taniguchi Tadatsugu, Takeda Kiyoshi, Hori Shohei, Ivanov Ivaylo I, Umesaki Yoshinori, Itoh Kikuji, Honda Kenya

    Science   1 - 5   2010.12

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    Language：English  

    Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
    <p>CD4+ T regulatory cells (Tregs), expressing the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota-particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-β (TGF-β) and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic IgE responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.</p>

    DOI： 10.1126/science.

  • Induction of lamina propria Th17 cells by intestinal commensal bacteria. Reviewed International journal

    Koji Atarashi, Takeshi Tanoue, Kenya Honda

    Vaccine   28 ( 50 )   8036 - 8   2010.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.vaccine.2010.09.026

  • Induction of lamina propria Th17 cells by intestinal commensal bacteria. Reviewed International journal

    Koji Atarashi, Takeshi Tanoue, Kenya Honda

    Vaccine   28 ( 50 )   8036 - 8   2010.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.vaccine.2010.09.026

  • A novel in vivo inducible dendritic cell ablation model in mice. Reviewed International journal

    Megumi Okuyama, Hisako Kayama, Koji Atarashi, Hiroyuki Saiga, Taishi Kimura, Ari Waisman, Masahiro Yamamoto, Kiyoshi Takeda

    Biochemical and biophysical research communications   397 ( 3 )   559 - 63   2010.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2010.05.157

  • A novel in vivo inducible dendritic cell ablation model in mice. Reviewed International journal

    Megumi Okuyama, Hisako Kayama, Koji Atarashi, Hiroyuki Saiga, Taishi Kimura, Ari Waisman, Masahiro Yamamoto, Kiyoshi Takeda

    Biochemical and biophysical research communications   397 ( 3 )   559 - 63   2010.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2010.05.157

  • Induction of intestinal Th17 cells by segmented filamentous bacteria. Reviewed International journal

    Ivaylo I Ivanov, Koji Atarashi, Nicolas Manel, Eoin L Brodie, Tatsuichiro Shima, Ulas Karaoz, Dongguang Wei, Katherine C Goldfarb, Clark A Santee, Susan V Lynch, Takeshi Tanoue, Akemi Imaoka, Kikuji Itoh, Kiyoshi Takeda, Yoshinori Umesaki, Kenya Honda, Dan R Littman

    Cell   139 ( 3 )   485 - 98   2009.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.cell.2009.09.033

  • Induction of intestinal Th17 cells by segmented filamentous bacteria. Reviewed International journal

    Ivaylo I Ivanov, Koji Atarashi, Nicolas Manel, Eoin L Brodie, Tatsuichiro Shima, Ulas Karaoz, Dongguang Wei, Katherine C Goldfarb, Clark A Santee, Susan V Lynch, Takeshi Tanoue, Akemi Imaoka, Kikuji Itoh, Kiyoshi Takeda, Yoshinori Umesaki, Kenya Honda, Dan R Littman

    Cell   139 ( 3 )   485 - 98   2009.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.cell.2009.09.033

  • NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection. Reviewed International journal

    Hisako Kayama, Ritsuko Koga, Koji Atarashi, Megumi Okuyama, Taishi Kimura, Tak W Mak, Satoshi Uematsu, Shizuo Akira, Hiroshi Takayanagi, Kenya Honda, Masahiro Yamamoto, Kiyoshi Takeda

    PLoS pathogens   5 ( 7 )   e1000514   2009.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.ppat.1000514

  • NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection. Reviewed International journal

    Hisako Kayama, Ritsuko Koga, Koji Atarashi, Megumi Okuyama, Taishi Kimura, Tak W Mak, Satoshi Uematsu, Shizuo Akira, Hiroshi Takayanagi, Kenya Honda, Masahiro Yamamoto, Kiyoshi Takeda

    PLoS pathogens   5 ( 7 )   e1000514   2009.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.ppat.1000514

  • Fra-1 negatively regulates lipopolysaccharide-mediated inflammatory responses. Reviewed International journal

    Hideaki Morishita, Fumiji Saito, Hisako Kayama, Koji Atarashi, Hirotaka Kuwata, Masahiro Yamamoto, Kiyoshi Takeda

    International immunology   21 ( 4 )   457 - 65   2009.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1093/intimm/dxp015

  • Fra-1 negatively regulates lipopolysaccharide-mediated inflammatory responses. Reviewed International journal

    Hideaki Morishita, Fumiji Saito, Hisako Kayama, Koji Atarashi, Hirotaka Kuwata, Masahiro Yamamoto, Kiyoshi Takeda

    International immunology   21 ( 4 )   457 - 65   2009.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1093/intimm/dxp015

  • ATP drives lamina propria T(H)17 cell differentiation. Reviewed International journal

    Koji Atarashi, Junichi Nishimura, Tatsuichiro Shima, Yoshinori Umesaki, Masahiro Yamamoto, Masaharu Onoue, Hideo Yagita, Naoto Ishii, Richard Evans, Kenya Honda, Kiyoshi Takeda

    Nature   455 ( 7214 )   808 - 12   2008.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature07240

  • ATP drives lamina propria T(H)17 cell differentiation. Reviewed International journal

    Koji Atarashi, Junichi Nishimura, Tatsuichiro Shima, Yoshinori Umesaki, Masahiro Yamamoto, Masaharu Onoue, Hideo Yagita, Naoto Ishii, Richard Evans, Kenya Honda, Kiyoshi Takeda

    Nature   455 ( 7214 )   808 - 12   2008.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature07240

  • TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi Reviewed International journal

    177 ( 10 )   7059 - 66   2006.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-γ production by T cells and NK cells. However, the involvement of innate immunity in host resistance to T. cruzi remains unclear. In the present study, we investigated host defense against T. cruzi by focusing on innate immunity. Macrophages and dendritic cells (DCs) from MyD88 -/-TRIF-/- mice, in which TLR-dependent activation of innate immunity was abolished, were defective in the clearance of T. cruzi and showed impaired induction of TFN-β during T. cruzi infection. Neutralization of IFN-β in MyD88-/- macrophages led to enhanced T. cruzi growth. Cells from MyD88-/-IFNAR1-/- mice also showed impaired T. cruzi clearance. Furthermore, both MyD88 -/-TRIF-/- and MyD88-/-IFNAR1-/- mice were highly susceptible to in vivo T. cruzi infection, highlighting the involvement of innate immune responses in T. cruzi infection. We further analyzed the molecular mechanisms for the IFN-β-mediated antitrypanosomal innate immune responses. MyD88-/-TRIF-/- and MyD88 -/-IFNAR1<

    DOI： 10.4049/jimmunol.177.10.7059

  • TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi Reviewed International journal

    177 ( 10 )   7059 - 66   2006.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-γ production by T cells and NK cells. However, the involvement of innate immunity in host resistance to T. cruzi remains unclear. In the present study, we investigated host defense against T. cruzi by focusing on innate immunity. Macrophages and dendritic cells (DCs) from MyD88 -/-TRIF-/- mice, in which TLR-dependent activation of innate immunity was abolished, were defective in the clearance of T. cruzi and showed impaired induction of TFN-β during T. cruzi infection. Neutralization of IFN-β in MyD88-/- macrophages led to enhanced T. cruzi growth. Cells from MyD88-/-IFNAR1-/- mice also showed impaired T. cruzi clearance. Furthermore, both MyD88 -/-TRIF-/- and MyD88-/-IFNAR1-/- mice were highly susceptible to in vivo T. cruzi infection, highlighting the involvement of innate immune responses in T. cruzi infection. We further analyzed the molecular mechanisms for the IFN-β-mediated antitrypanosomal innate immune responses. MyD88-/-TRIF-/- and MyD88 -/-IFNAR1<

    DOI： 10.4049/jimmunol.177.10.7059

  • IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation Reviewed International journal

    24 ( 1 )   41 - 51   2006.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Toll-like receptor (TLR)-mediated immune responses are downregulated by several mechanisms that affect signaling pathways. However, it remains elusive how TLR-mediated gene expression is differentially modulated. Here, we show that IκBNS, a TLR-inducible nuclear IκB protein, negatively regulates induction of a subset of TLR-dependent genes through inhibition of NF-κB activity. IκBNS-deficient macrophages and dendritic cells show increased TLR-mediated expression of genes such as IL-6 and IL-12p40, which are induced late after TLR stimulation. In contrast, IκBNS-deficient cells showed normal induction of genes that are induced early or induced via IRF-3 activation. LPS stimulation of IκBNS-deficient macrophages prolonged NF-κB activity at the specific promoters, indicating that IκBNS mediates termination of NF-κB activity at selective gene promoters. Moreover, IκBNS-deficient mice are highly susceptible to LPS-induced endotoxin shock and intestinal inflammation. Thus, IκBNS regulates inflammatory responses by inhibiting the induction of a subset of TLR-dependent genes through modulation of NF-κB activity. © 2006 Elsevier Inc.</p>

    DOI： 10.1016/j.immuni.2005.11.004

  • IκBNS inhibits induction of a subset of toll-like receptor-dependent genes and limits inflammation Reviewed International journal

    24 ( 1 )   41 - 51   2006.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    <p>Toll-like receptor (TLR)-mediated immune responses are downregulated by several mechanisms that affect signaling pathways. However, it remains elusive how TLR-mediated gene expression is differentially modulated. Here, we show that IκBNS, a TLR-inducible nuclear IκB protein, negatively regulates induction of a subset of TLR-dependent genes through inhibition of NF-κB activity. IκBNS-deficient macrophages and dendritic cells show increased TLR-mediated expression of genes such as IL-6 and IL-12p40, which are induced late after TLR stimulation. In contrast, IκBNS-deficient cells showed normal induction of genes that are induced early or induced via IRF-3 activation. LPS stimulation of IκBNS-deficient macrophages prolonged NF-κB activity at the specific promoters, indicating that IκBNS mediates termination of NF-κB activity at selective gene promoters. Moreover, IκBNS-deficient mice are highly susceptible to LPS-induced endotoxin shock and intestinal inflammation. Thus, IκBNS regulates inflammatory responses by inhibiting the induction of a subset of TLR-dependent genes through modulation of NF-κB activity. © 2006 Elsevier Inc.</p>

    DOI： 10.1016/j.immuni.2005.11.004

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MISC

  • 無菌コモンマーモセットの作出

    井上 貴史, 植野 昌未, 野津 量子, 岡原 則夫, 岡橋 伸幸, 佐藤 賢哉, 上田 政広, 新 幸二, 諫山 純, 青戸 良賢, 川島 祐介, 菊池 理加, 黒滝 陽子, 峰重 隆幸, 圦本 晃海, 板谷 佳織, 田之上 大, 中畑 龍俊, 塩田 淳, 有田 誠, 本田 賢也, 佐々木 えりか

    無菌生物   52 ( 2 )   25 - 26   2022.12   （ ISSN:0910-0903 ）

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    Language：Japanese   Publisher：日本無菌生物ノートバイオロジー学会  

    無菌霊長類を用いた腸内微生物叢研究の展開をめざして,我々は小型の霊長類種のコモンマーモセットにおいて無菌動物の作出とその研究応用のための技術開発を進めている.妊娠個体の準備からビニールアイソレータ内の無菌環境下での帝王切開による産仔獲得,人工哺育,育成までの一連の技術確立を進めて無菌マーモセットの作出を試みた.その結果,糞便の培養検査により生菌が検出されない無菌マーモセット個体の作出に成功し,最長で24ヵ月齢まで培養検査陰性の維持に至った.獲得したマーモセット個体では,糞便中の二次胆汁酸の欠如や,分泌型IgAの低濃度,糞便・血漿のプロテオーム解析での免疫関連のタンパク質の低発現,造影レントゲン検査のよる盲腸拡大が観察され,無菌動物としての特性が示唆された.今後は,作出した無菌マーモセットの繁殖を試みるとともに,作出技術を洗練させて研究利用のための安定供給体制を確立していきたい.(著者抄録)

  • 【腸内細菌と免疫、その最新情報】腸内細菌とTH1/TH2/CD8+T細胞免疫応答

    田之上 大, 新 幸二

    腸内細菌学雑誌   36 ( 1 )   13 - 20   2022.1   （ ISSN:1343-0882 ）

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    Language：Japanese   Publisher：(公財)腸内細菌学会  

    T細胞は抗原特異的な免疫応答において中心的役割を担う免疫細胞であり、その分化・機能に腸内細菌が関与することが知られている。T細胞のうちαβT細胞受容体を発現するT細胞はCD4T細胞およびCD8T細胞に大別される。CD4T細胞のうちTH1細胞と呼ばれるサブセットは細胞内寄生細菌に対する免疫応答に重要であるとともに、その過剰な活性化は自己免疫疾患の発症・増悪に関与する。一方、TH2細胞サブセットは寄生虫感染防御応答に重要であるかたわら、花粉症や喘息などのアレルギー応答の増悪にも関与する。また、CD8T細胞は病原性細菌・ウイルスやがん免疫応答に重要な役割を担っている。この記事では、これらTH1、TH2およびCD8T細胞応答とその関連疾患に関与する腸内細菌を紹介する。(著者抄録)

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