Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis

Liang Chen, Mingming Sun, Wei Wu, Wenjing Yang, Xiangsheng Huang, Yi Xiao, Chunyan Ma, Leiqi Xu, Suxia Yao, Zhanju Liu, Yingzi Cong

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1450-1461
Number of pages12
JournalInflammatory bowel diseases
Volume25
Issue number9
DOIs
StatePublished - Aug 20 2019

Fingerprint

Th17 Cells
Th1 Cells
Butyrates
Microbiota
Colitis
Cell Differentiation
T-Lymphocytes
Interleukin-10
B-Lymphocytes
Volatile Fatty Acids
Immunodominant Epitopes
Proteins
Histone Deacetylases
Interleukin-17
Inflammatory Bowel Diseases

Keywords

  • butyrate
  • colitis
  • IL-10
  • Th1 cells
  • Th17 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis. / Chen, Liang; Sun, Mingming; Wu, Wei; Yang, Wenjing; Huang, Xiangsheng; Xiao, Yi; Ma, Chunyan; Xu, Leiqi; Yao, Suxia; Liu, Zhanju; Cong, Yingzi.

In: Inflammatory bowel diseases, Vol. 25, No. 9, 20.08.2019, p. 1450-1461.

Research output: Contribution to journalArticle

Chen, Liang ; Sun, Mingming ; Wu, Wei ; Yang, Wenjing ; Huang, Xiangsheng ; Xiao, Yi ; Ma, Chunyan ; Xu, Leiqi ; Yao, Suxia ; Liu, Zhanju ; Cong, Yingzi. / Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis. In: Inflammatory bowel diseases. 2019 ; Vol. 25, No. 9. pp. 1450-1461.
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T1 - Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells' Differentiation and Function in Induction of Colitis

AU - Chen, Liang

AU - Sun, Mingming

AU - Wu, Wei

AU - Yang, Wenjing

AU - Huang, Xiangsheng

AU - Xiao, Yi

AU - Ma, Chunyan

AU - Xu, Leiqi

AU - Yao, Suxia

AU - Liu, Zhanju

AU - Cong, Yingzi

PY - 2019/8/20

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N2 - 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.

AB - 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.

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