GPR120 Inhibits Colitis Through Regulation of CD4+ T Cell Interleukin 10 Production

Wenjing Yang, Han Liu, Leiqi Xu, Tianming Yu, Xiaojing Zhao, Suxia Yao, Qihong Zhao, Sean Barnes, Steven M. Cohn, Sara M. Dann, Hongjie Zhang, Xiuli Zuo, Yanqing Li, Yingzi Cong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background & Aims: G protein–coupled receptor (GPR) 120 has been implicated in regulating metabolic syndromes with anti-inflammatory function. However, the role of GPR120 in intestinal inflammation is unknown. Here, we investigated whether and how GPR120 regulates CD4+ T cell function to inhibit colitis development. Methods: Dextran sodium sulfate (DSS)–induced colitis model, Citrobacter rodentium infection model, and CD4+ T cell adoptive transfer model were used to analyze the role of GPR120 in regulating colitis development. The effect of GPR120 on CD4+ T cell functions was analyzed by RNA sequencing, flow cytometry, and Seahorse metabolic assays. Mice were administered GPR120 agonist for investigating the potential of GPR120 agonist in preventing and treating colitis. Results: Deficiency of GPR120 in CD4+ T cells resulted in more severe colitis in mice upon dextran sodium sulfate insult and enteric infection. Transfer of GPR120-deficient CD4+CD45Rbhi T cells induced more severe colitis in Rag–/– mice with lower intestinal interleukin (IL) 10+CD4+ T cells. Treatment with the GPR120 agonist CpdA promoted CD4+ T cell production of IL10 by up-regulating Blimp1 and enhancing glycolysis, which was regulated by mTOR. GPR120 agonist-treated wild-type, but not IL10-deficient and Blimp1-deficient, T helper 1 cells induced less severe colitis. Furthermore, oral administration of GPR120 agonist protected mice from intestinal inflammation in both prevention and treatment schemes. Gpr120 expression was positively correlated with Il10 expression in the human colonic mucosa, including patients with inflammatory bowel diseases. Conclusions: Our findings show the role of GPR120 in regulating intestinal CD4+ T cell production of IL10 to inhibit colitis development, which identifies GPR120 as a potential therapeutic target for treating inflammatory bowel diseases.

Original languageEnglish (US)
Pages (from-to)150-165
Number of pages16
JournalGastroenterology
Volume162
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Blimp1
  • Effector CD4 T cells
  • Glycolysis
  • Inflammatory Bowel Diseases
  • Intestinal Homeostasis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint

Dive into the research topics of 'GPR120 Inhibits Colitis Through Regulation of CD4<sup>+</sup> T Cell Interleukin 10 Production'. Together they form a unique fingerprint.

Cite this