Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, et. al.Nature 2013 December; 504: 446–450.
Speaker: Yi-Wen Liu (劉怡彣) Time: 13:00~14:00, Sep. 24, 2014
Commentator: Dr. Jenn-Wei Chen (陳振暐 老師) Place: Room 601
Abstract
Many studies have suggested that gut commensal microbes can shape the mucosal immune system by regulating the differentiation of colonic regulatory T cells (Treg cells). Previous studies have demonstrated that germ-free mice have unusually enlarged caecum due to the accumulation of hydrated dietary fibre components, but caecal size can be normalized by colonization with chloroform resistant bacteria (CRB). Therefore, CRB-derived dietary fibre metabolites could be responsible for the induction of colonic Treg cells [1]. In this study, the authors found that in CRB associated high-fibre diet-fed mice (CRB-HFD), the expression of peripherally generated Treg cell population was significantly increased [2]. Next, the authors discovered that the amount of caecalshort-chain fatty acids (SCFAs) was higher in CRB-HFD than in CRB- low-fibre diet mice (CRB-LFD). Among these SCFAs, butyrate significantly increased the frequency of Foxp3+ cells. To corroborate the role of butyrate in Treg cell induction, specific pathogen-free mice (SPF) were fed modified diets containing butylated high-amylose maize starches (HAMSB) to increase the luminal levels of the butyrate. Colonic Treg cells were significantly augmented when the diet contained HAMSB in SPF mice. However, HAMSB did not increase Treg cells under germ free conditions, suggesting that the presence of commensal bacteria is a prerequisite for Treg cell induction. Further probing revealed that butyrate enhanced histone H3 acetylation in the enhancer and promoter regions of the Foxp3 gene locus. Finally, the authors confirmed that butyrate-induced Treg cells ameliorated the development of colitis induced by adoptive transfer of CD4+ CD45RBhi T cells in Rag1-/- mice. In conclusion, this finding link butyrate to commensal microbe-mediated induction of functional Treg cells in the colonic mucosa and provide molecular insight into the therapeutic application of butyrate.
References
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2. Thornton, A. M. et al. 2010. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441.