Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

被引:2845
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
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
收藏
页码:337 / 341
页数:5
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共 25 条
  • [11] Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
    Ivanov, Ivaylo I.
    Atarashi, Koji
    Manel, Nicolas
    Brodie, Eoin L.
    Shima, Tatsuichiro
    Karaoz, Ulas
    Wei, Dongguang
    Goldfarb, Katherine C.
    Santee, Clark A.
    Lynch, Susan V.
    Tanoue, Takeshi
    Imaoka, Akemi
    Itoh, Kikuji
    Takeda, Kiyoshi
    Umesaki, Yoshinori
    Honda, Kenya
    Littman, Dan R.
    [J]. CELL, 2009, 139 (03) : 485 - 498
  • [12] Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse
    Kamanaka, Masahito
    Kim, Sean T.
    Wan, Yisong Y.
    Sutterwala, Fayyaz S.
    Lara-Tejero, Maria
    Galan, Jorge E.
    Harhaj, Ed
    Flavell, Richard A.
    [J]. IMMUNITY, 2006, 25 (06) : 941 - 952
  • [13] Lactobacillus reuteri-induced Regulatory T cells Protect against an Allergic Airway Response in Mice
    Karimi, Khalil
    Inman, Mark D.
    Bienenstock, John
    Forsythe, Paul
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2009, 179 (03) : 186 - 193
  • [14] Bacterial strain-specific induction of Foxp3+T regulatory cells is protective in murine allergy models
    Lyons, A.
    O'Mahony, D.
    O'Brien, F.
    MacSharry, J.
    Sheil, B.
    Ceddia, M.
    Russell, W. M.
    Forsythe, P.
    Bienenstock, J.
    Kiely, B.
    Shanahan, F.
    O'Mahony, L.
    [J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2010, 40 (05) : 811 - 819
  • [15] Interactions between commensal intestinal bacteria and the immune system
    Macpherson, AJ
    Harris, NL
    [J]. NATURE REVIEWS IMMUNOLOGY, 2004, 4 (06) : 478 - 485
  • [16] Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10
    Maynard, Craig L.
    Harrington, Laurie E.
    Janowski, Karen M.
    Oliver, James R.
    Zindl, Carlene L.
    Rudensky, Alexander Y.
    Weaver, Casey T.
    [J]. NATURE IMMUNOLOGY, 2007, 8 (09) : 931 - 941
  • [17] Gut flora antigens are not important in the maintenance of regulatory T cell heterogeneity and homeostasis
    Min, Booki
    Thornton, Angela
    Caucheteux, Stephan M.
    Younes, Souheil-Antoine
    Oh, Keunhee
    Hu-Li, Jane
    Paul, William E.
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (07) : 1916 - 1923
  • [18] 16S rRNA gene sequence-based analysis of clostridia related to conversion of germfree mice to the normal state
    Momose, Y.
    Maruyama, A.
    Iwasaki, T.
    Miyamoto, Y.
    Itoh, K.
    [J]. JOURNAL OF APPLIED MICROBIOLOGY, 2009, 107 (06) : 2088 - 2097
  • [19] Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota
    Round, June L.
    Mazmanian, Sarkis K.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (27) : 12204 - 12209
  • [20] The gut microbiota shapes intestinal immune responses during health and disease
    Round, June L.
    Mazmanian, Sarkis K.
    [J]. NATURE REVIEWS IMMUNOLOGY, 2009, 9 (05) : 313 - 323