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

Yadong Ge, Mingming Sun, Wei Wu, Caiyun Ma, Cui Zhang, Chong He, Junxiang Li, Yingzi Cong, Dekui Zhang, Zhanju Liu

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)109-120
    Number of pages12
    JournalJournal of Autoimmunity
    Volume101
    DOIs
    StatePublished - Jul 2019

    Keywords

    • CD4 T cells
    • Ets-1
    • Inflammatory bowel disease
    • Th1
    • Th17
    • miR-125a

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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