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

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

来源：Journal of Autoimmunity, 2019, 101: 109-120.

DOI：10.1016/j.jaut.2019.04.014

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

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-gamma, TNF-alpha and IL-17A. RNA-seq analysis of miR-125a(-/-) CD4(+) T cells revealed enhanced genes (e.g., Stat1, Stat3, ROR gamma t, 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.

• 单位
  兰州大学; 同济大学; 2; 四川省医学科学院（四川省人民医院）; 电子科技大学; 北京中医药大学