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Science 331 (6015): 337-341

Copyright © 2011 by the American Association for the Advancement of Science

Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

Koji Atarashi,1,* Takeshi Tanoue,1,* Tatsuichiro Shima,2 Akemi Imaoka,2 Tomomi Kuwahara,3 Yoshika Momose,4 Genhong Cheng,5 Sho Yamasaki,6 Takashi Saito,6 Yusuke Ohba,7 Tadatsugu Taniguchi,1 Kiyoshi Takeda,8 Shohei Hori,9 Ivaylo I. Ivanov,10 Yoshinori Umesaki,2 Kikuji Itoh,4 Kenya Honda1,11,{dagger}

Abstract: CD4+ T regulatory cells (Tregs), which express 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 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 immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

1 Department of Immunology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
2 Yakult Central Institute for Microbiological Research, Tokyo 186-8650, Japan.
3 Department of Molecular Bacteriology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan.
4 Department of Veterinary Public Health, University of Tokyo, Tokyo 113-8657, Japan.
5 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
6 Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
7 Laboratory of Pathophysiology and Signal Transduction, Hokkaido University, Graduate School of Medicine, Sapporo 060-8638, Japan.
8 Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
9 Research Unit for Immune Homeostasis, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
10 Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
11 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kenya{at}m.u-tokyo.ac.jp

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