Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis. Issue 9 (27th March 2019)

• Record Type: Journal Article
• Authors: Chen, Liang; Sun, Mingming; Wu, Wei; Yang, Wenjing; Huang, Xiangsheng; Xiao, Yi; Ma, Chunyan; Xu, Leiqi; Yao, Suxia; Liu, Zhanju; Cong, Yingzi
• Is Part Of: Inflammatory bowel diseases. Volume 25:Issue 9(2019)
• Page Start: 1450
• Page End: 1461
• Publication Date: 2019-03-27
• Subjects: butyrate -- Th1 cells -- Th17 cells -- IL-10 -- colitis; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izz046
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Background: How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated. Methods: CBir1, an immunodominant microbiota antigen, transgenic T cells were treated with butyrate under various T-cell polarization conditions to investigate butyrate regulation of T-cell differentiation and the mechanism involved. Transfer of butyrate-treated CBir T cells into Rag1 -/- mice was performed to study the in vivo role of such T cells in inducing colitis. Results: Although butyrate promoted Th1 cell development by promoting IFN-γ and T-bet expression, it inhibited Th17 cell development by suppressing IL-17, Rorα, and Rorγt expression. Interestingly, butyrate upregulated IL-10 production in T cells both under Th1 and Th17 cell conditions. Furthermore, butyrate induced T-cell B-lymphocyte-induced maturation protein 1 (Blimp1) expression, and deficiency of Blimp1 in T cells impaired the butyrate upregulation of IL-10 production, indicating that butyrate promotes T-cell IL-10 production at least partially through Blimp1. Rag1 -/- mice transferred with butyrate-treated T cells demonstrated less severe colitis, compared with transfer of untreated T cells, and administration of anti-IL-10R antibody exacerbated colitis development in Rag -/- mice that had received butyrate-treated T cells. Mechanistically, the effects of butyrate on the development of Th1 cells was through inhibition of histone deacetylase but was independent of GPR43. Conclusions: These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease. Abstract : Gut microbiota–derived butyrate differentially regulates Th1 and Th17 cell differentiation and promotes T-cell IL-10 production during their differentiation, leading to inhibition of the potential of these T cells in induction of colitis.