期刊
NATURE
卷 504, 期 7480, 页码 446-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12721
关键词
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资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology [24117524, 21022049, 20113003]
- The Japan Society for the Promotion of Science [24890293, 252667, 24380072, 24658129, 22689017, 21390155]
- The Japan Science and Technology Agency
- RIKEN
- RIKEN RCAI Young Chief Investigator program
- Institute for Fermentation, Osaka
- Mishima Kaiun Memorial Foundation
- The Takeda Science Foundation
- The Mitsubishi Foundation
- The Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [24117723, 21390155, 25660101, 13J02667, 25118733, 23390123, 21022049, 22689017, 23780131, 24890293, 25293114, 25513012, 24117524, 24658129, 13J05482] Funding Source: KAKEN
Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell(1-5). Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (T-reg) cells, which have a central role in the suppression of inflammatory and allergic responses(3). However, the molecular mechanisms by which commensal microbes induce colonic T-reg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic T-reg 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 T-reg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of T-reg 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 T-reg-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 T-reg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
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