Abstract
Irregular CD4+ effector T cell responses play an essential role in the intestinal inflammation, while IL-10 produced by effector T cells limits their pathogenesis to maintain the intestinal homeostasis. Dietary free fatty acids are actively involved in regulating immune responses, and mammalian G protein-coupled receptor (GPR) 120, a receptor for long-chain fatty acids, has been implicated in metabolic syndrome. However, the effect of GPR120 on intestinal homeostasis is still unknown. Here, we showed that deficiency of GPR120 resulted in more severe colitis in mice induced by dextran sodium sulfate (DSS) and Citrobacter Rodentium. Interestingly, CD4+ T cells expressed a high level of GPR120, and mice specifically lacking GPR120 in CD4+ T cells were more susceptible to DSS-induced colitis. Besides, GPR120-deficient CD45Rbhi CD4+ cells are more colitogenic in Rag-/- mice, in which IL-17 and IFNg producing CD4+ T cells were increased but IL-10 production by CD4+ T cells was reduced. Furthermore, CpdA, the GPR120 agonist, promoted CD4+ T effector cell production of IL-10 through upregulating Blimp1 and inducing glycolysis, which were regulated by mTOR pathway. Besides, docosahexaenoic acid, a dietary long-chain fatty acid, also upregulated the IL-10 production in CD4+ T cells. Additionally, GPR120 agonist-treated Th1 effector cells induced less severe colitis, whereas this protection was absent in Blimp1-deficient Th1 cells. Importantly, oral administration of CpdA protected mice against intestinal inflammation. Thus, our findings demonstrate the roles of dietary fatty acids receptor GPR120 in regulating intestinal CD4+ T cell production of IL-10 and intestinal homeostasis.
Tu1873 A Population of Cytokine Deficient CD4+ T Cells is Associated With Increased Body Mass Index and Intestinal Inflammation
