RRC ID 29487
著者 Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H.
タイトル Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
ジャーナル Nature
Abstract Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
巻・号 504(7480)
ページ 446-50
公開日 2013-12-19
DOI 10.1038/nature12721
PII nature12721
PMID 24226770
MeSH Acetylation / drug effects Adoptive Transfer Animals Butyrates / analysis Butyrates / metabolism* Butyrates / pharmacology Cell Differentiation* / drug effects Colitis / drug therapy Colitis / pathology Colon / cytology Colon / immunology* Colon / metabolism Colon / microbiology* Conserved Sequence Female Fermentation* Forkhead Transcription Factors / genetics Germ-Free Life Histones / metabolism Homeostasis / drug effects Intestinal Mucosa / cytology Intestinal Mucosa / immunology Lymphocyte Count Magnetic Resonance Spectroscopy Male Metabolome Mice Promoter Regions, Genetic / drug effects Symbiosis* T-Lymphocytes, Regulatory / cytology* T-Lymphocytes, Regulatory / drug effects T-Lymphocytes, Regulatory / immunology
IF 42.779
引用数 1732
WOS 分野 IMMUNOLOGY
リソース情報
一般微生物 JCM 5827