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

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 Dann-Grice, Qihong Zhao, Zhanju Liu, Yingzi Cong

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article number3555
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

homeostasis
Th1 Cells
Volatile Fatty Acids
Microbiota
fatty acids
Interleukin-10
Homeostasis
Colitis
cells
antigens
Metabolites
Antigens
metabolites
induction
T-cells
Lymphocytes
G-Protein-Coupled Receptors
proteins
effectors
lymphocytes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. / Sun, Mingming; Wu, Wei; Chen, Liang; Yang, Wenjing; Huang, Xiangsheng; Ma, Caiyun; Chen, Feidi; Xiao, Yi; Zhao, Ye; Ma, Chunyan; Yao, Suxia; Carpio, Victor H.; Dann-Grice, Sara; Zhao, Qihong; Liu, Zhanju; Cong, Yingzi.

In: Nature Communications, Vol. 9, No. 1, 3555, 01.12.2018.

Research output: Contribution to journalArticle

Sun, M, Wu, W, Chen, L, Yang, W, Huang, X, Ma, C, Chen, F, Xiao, Y, Zhao, Y, Ma, C, Yao, S, Carpio, VH, Dann-Grice, S, Zhao, Q, Liu, Z & Cong, Y 2018, 'Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis', Nature Communications, vol. 9, no. 1, 3555. https://doi.org/10.1038/s41467-018-05901-2
Sun, Mingming ; Wu, Wei ; Chen, Liang ; Yang, Wenjing ; Huang, Xiangsheng ; Ma, Caiyun ; Chen, Feidi ; Xiao, Yi ; Zhao, Ye ; Ma, Chunyan ; Yao, Suxia ; Carpio, Victor H. ; Dann-Grice, Sara ; Zhao, Qihong ; Liu, Zhanju ; Cong, Yingzi. / Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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