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Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis

Author

Listed:
  • Mingming Sun

    (Tongji University
    The University of Texas Medical Branch)

  • Wei Wu

    (Tongji University
    The University of Texas Medical Branch)

  • Liang Chen

    (Tongji University
    The University of Texas Medical Branch)

  • Wenjing Yang

    (Tongji University
    The University of Texas Medical Branch)

  • Xiangsheng Huang

    (The University of Texas Medical Branch)

  • Caiyun Ma

    (Tongji University)

  • Feidi Chen

    (University of Texas Medical Branch)

  • Yi Xiao

    (The University of Texas Medical Branch)

  • Ye Zhao

    (The University of Texas Medical Branch)

  • Chunyan Ma

    (The University of Texas Medical Branch)

  • Suxia Yao

    (The University of Texas Medical Branch)

  • Victor H. Carpio

    (The University of Texas Medical Branch)

  • Sara M. Dann

    (The University of Texas Medical Branch)

  • Qihong Zhao

    (Bristol-Myers Squibb)

  • Zhanju Liu

    (Tongji University)

  • Yingzi Cong

    (The University of Texas Medical Branch
    University of Texas Medical Branch)

Abstract

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.

Suggested Citation

  • 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 , 2018. "Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05901-2
    DOI: 10.1038/s41467-018-05901-2
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    Cited by:

    1. Xudong Tang & Yangyang Shang & Hong Yang & Yalan Song & Shan Li & Yusi Qin & Jingyi Song & Kang Chen & Yang Liu & Dinglin Zhang & Lei Chen, 2024. "Targeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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