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

7 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 1 2019

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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