Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells

Y Furusawa, Y Obata, S Fukuda, TA Endo, G Nakato… - Nature, 2013 - nature.com
Y Furusawa, Y Obata, S Fukuda, TA Endo, G Nakato, D Takahashi, Y Nakanishi, C Uetake…
Nature, 2013nature.com
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 …
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+CD45RBhi 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.
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