刘占举等:肠道菌群产物如何调节Th1缓解肠道炎症
  • GPR43是肠道菌群产物短链脂肪酸(SCFA)的受体之一;
  • GPR43-/-菌群抗原特异的Th1细胞,可在受体小鼠中引起更严重的结肠炎,说明Th1中SCFA-GPR43互作可抑制结肠炎;
  • SCFA经GPR43激活Th1中STAT3和mTOR通路,使转录因子Blimp-1表达上调,从而促进Th1生成IL-10,缓解小鼠结肠炎;
  • 用IL-10受体抗体处理、在Th1中敲除Blimp-1从而减少IL10生成,均可导致小鼠结肠炎加重;
  • SCFA促进IBD患者T细胞生成IL-10,小鼠口服SCFA可缓解DSS诱导的结肠炎。
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mildbreeze
Nature Communications刚刚上线来自同济大学附属第十人民医院刘占举团队与德克萨斯大学加尔维斯顿医学分部Yingzi Cong团队合作主导的最新研究。该研究通过小鼠和细胞实验,揭示了肠道菌群代谢物短链脂肪酸(SCFA)是如何调节效应T细胞中的Th1细胞,从而维持肠道稳态、抑制过度炎症的。这些发现对研究菌群产物对宿主免疫的调控,以及炎症性肠病的治疗,均有参考价值。
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Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis

菌群衍生的短链脂肪酸促进Th1细胞生成IL-10以维持肠道稳态

10.1038/s41467-018-05901-2

2018-09-03, Article

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T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43 CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1 Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis.

First Authors:
Mingming Sun,Wei Wu,Liang Chen

Correspondence Authors:
Zhanju Liu,Yingzi Cong

All Authors:
Mingming Sun,Wei Wu,Liang Chen,Wenjing Yang,Xiangsheng Huang,Caiyun Ma,Feidi Chen,Yi Xiao,Ye Zhao,Chunyan Ma,Suxia Yao,Victor H Carpio,Sara M Dann,Qihong Zhao,Zhanju Liu,Yingzi Cong

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