MicroRNA-125a suppresses intestinal mucosal inflammation through targeting ETS-1 in patients with inflammatory bowel diseases.

MicroRNA (miR)-125a is highly expressed in T cells and regulates the functions of Treg through the IL-6-STAT3 signaling pathway. However, the role of miR-125a in regulating immune responses in intestinal mucosa of patients with inflammatory bowel diseases (IBD) is still not understood. Here we showed that miR-125a expression was decreased in PBMC and inflamed intestinal mucosa from IBD patients compared with that in healthy controls. Transduction with LV-miR-125a into IBD CD4+ T cells could significantly inhibit proinflammatory cytokine production, including IFN-γ, TNF-α and IL-17A. RNA-seq analysis of miR-125a−/− CD4+ T cells revealed enhanced genes (e.g., Stat1 , Stat3 , RORγt , Irf4 , Klf13) in T cell activation and effector pathways, while ETS-1 as its functional target promoted IBD CD4+ T cell differentiation into Th1 cells. Consistently, miR-125a−/− mice developed more severe colitis induced by TNBS compared with WT mice. Thus, our data suggest that miR-125a protects intestinal mucosa from inflammatory injury and that ETS-1 as its target participates in the pathogenesis of IBD. • miR-125a expression is decreased in inflamed mucosa and peripheral blood from IBD patients. • miR-125a inhibits Th1/Th17 cell differentiation and TNF-α production in IBD. • IL-6 and TNF-α downregulate miR-125a expression in CD4+ T cells from IBD patients. • miR-125a restrains Th1 cell differentiation and TNF-α production of CD4+ T cells by targeting ETS-1. • miR-125a deficient mice develop more severe colitis induced by TNBS. [ABSTRACT FROM AUTHOR]