Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

被引：2905

作者：

Atarashi, Koji ^{[1
]}

Tanoue, Takeshi ^{[1
]}

Shima, Tatsuichiro ^{[2
]}

Imaoka, Akemi ^{[2
]}

Kuwahara, Tomomi ^{[3
]}

Momose, Yoshika ^{[4
]}

Cheng, Genhong ^{[5
]}

Yamasaki, Sho ^{[6
]}

Saito, Takashi ^{[6
]}

Ohba, Yusuke ^{[7
]}

Taniguchi, Tadatsugu ^{[1
]}

Takeda, Kiyoshi ^{[8
]}

Hori, Shohei ^{[9
]}

Ivanov, Ivaylo I. ^{[10
]}

Umesaki, Yoshinori ^{[2
]}

Itoh, Kikuji ^{[4
]}

Honda, Kenya ^{[1
,11
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Immunol, Tokyo 1130033, Japan

[2] Yakult Cent Inst Microbiol Res, Tokyo 1868650, Japan

[3] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Mol Bacteriol, Tokushima 7708503, Japan

[4] Univ Tokyo, Dept Vet Publ Hlth, Tokyo 1138657, Japan

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[6] RIKEN Res Ctr Allergy & Immunol, Lab Cell Signaling, Kanagawa 2300045, Japan

[7] Hokkaido Univ, Grad Sch Med, Lab Pathophysiol & Signal Transduct, Sapporo, Hokkaido 0608638, Japan

[8] Osaka Univ, Grad Sch Med, Lab Immune Regulat, Suita, Osaka 5650871, Japan

[9] RIKEN Res Ctr Allergy & Immunol, Res Unit Immune Homeostasis, Kanagawa 2300045, Japan

[10] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA

[11] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

SCIENCE | 2011年 / 331卷 / 6015期

关键词：

SEGMENTED FILAMENTOUS BACTERIA; INTESTINAL IMMUNE-RESPONSES; MICROBIOTA; INTERLEUKIN-10; HOMEOSTASIS; COLITIS; INFLAMMATION; SYSTEM; BETA;

D O I：

10.1126/science.1198469

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CD4(+) T regulatory cells (T-regs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T-regs 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 T-reg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-beta and affected Foxp3(+) T-reg 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.

引用

页码：337 / 341

页数：5

共 25 条

[1] Regulatory T Cells Reinforce Intestinal Homeostasis [J].

Barnes, Michael J. ;

Powrie, Fiona .

IMMUNITY, 2009, 31 (03) :401-411

[2] Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 [J].

Boirivant, M ;

Fuss, IJ ;

Chu, A ;

Strober, W .

JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1929-1939

[3] Authentic matrix vesicles contain active metalloproteases (MMP) -: A role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-β [J].

D'Angelo, M ;

Billings, PC ;

Pacifici, M ;

Leboy, PS ;

Kirsch, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) :11347-11353

[4] Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-β-bearing regulatory cells [J].

Di Giacinto, C ;

Marinaro, M ;

Sanchez, M ;

Strober, W ;

Boirivant, M .

JOURNAL OF IMMUNOLOGY, 2005, 174 (06) :3237-3246

[5] Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases [J].

Frank, Daniel N. ;

Amand, Allison L. St. ;

Feldman, Robert A. ;

Boedeker, Edgar C. ;

Harpaz, Noam ;

Pace, Norman R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (34) :13780-13785

[6] The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses [J].

Gaboriau-Routhiau, Valerie ;

Rakotobe, Sabine ;

Lecuyer, Emelyne ;

Mulder, Imke ;

Lan, Annaig ;

Bridonneau, Chantal ;

Rochet, Violaine ;

Pisi, Annamaria ;

De Paepe, Marianne ;

Brandi, Giovanni ;

Eberl, Gerard ;

Snel, Johannes ;

Kelly, Denise ;

Cerf-Bensussan, Nadine .

IMMUNITY, 2009, 31 (04) :677-689

[7] Homeostasis and Inflammation in the Intestine [J].

Garrett, Wendy S. ;

Gordon, Jeffrey I. ;

Glimcher, Laurie H. .

CELL, 2010, 140 (06) :859-870

[8] Commensal DNA Limits Regulatory T Cell Conversion and Is a Natural Adjuvant of Intestinal Immune Responses [J].

Hall, Jason A. ;

Bouladoux, Nicolas ;

Sun, Cheng Ming ;

Wohlfert, Elizabeth A. ;

Blank, Rebecca B. ;

Zhu, Qing ;

Grigg, Michael E. ;

Berzofsky, Jay A. ;

Belkaid, Yasmine .

IMMUNITY, 2008, 29 (04) :637-649

[9] CHARACTERIZATION OF CLOSTRIDIA ISOLATED FROM FECES OF LIMITED FLORA MICE AND THEIR EFFECT ON CECAL SIZE WHEN ASSOCIATED WITH GERM-FREE MICE [J].

ITOH, K ;

MITSUOKA, T .

LABORATORY ANIMALS, 1985, 19 (02) :111-118

[10] Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small Intestine [J].

Ivanov, Ivaylo I. ;

Frutos, Rosa de Llanos ;

Manel, Nicolas ;

Yoshinaga, Keiji ;

Rifkin, Daniel B. ;

Sartor, R. Balfour ;

Finlay, B. Brett ;

Littman, Dan R. .

CELL HOST & MICROBE, 2008, 4 (04) :337-349

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