Induction of autophagy in Cx3cr1⁺ mononuclear cells limits IL-23/IL-22 axis-mediated intestinal fibrosis.

ABSTRACT: Intestinal fibrosis is an excessive proliferation of myofibroblasts and deposition of collagen, a condition frequently seen in Crohn's disease (CD). The mechanism underlying myofibroblast hyper-proliferation in CD needs to be better understood. In this report, we found that mTOR inhibitor rapamycin or mTOR deletion in CX3Cr1⁺ mononuclear phagocytes inhibits expression of interleukin (IL)-23, accompanied by reduced intestinal production of IL-22 and ameliorated fibrosis in the TNBS-induced fibrosis mouse model. This inhibition of IL-23 expression is associated with elevated autophagy activity. Ablating the autophagy gene Atg7 increases the expression of IL-23, leading to increased expression of IL-22 and increased fibrosis. Both induction of IL-22 and intestinal fibrosis occurred

SUBMITTER: Mathur R 

PROVIDER: S-EPMC6927046 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature