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

Yadong Ge1, Mingming Sun1, Wei Wu1

  • 1Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.

Journal of Autoimmunity
|April 25, 2019
PubMed

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.

Keywords:
CD4(+) T cellsEts-1Inflammatory bowel diseaseTh1Th17miR-125a

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