Journal
JOURNAL OF AUTOIMMUNITY
Volume 101, Issue -, Pages 109-120Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.04.014
Keywords
miR-125a; Inflammatory bowel disease; CD4(+) T cells; Ets-1; Th1; Th17
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Funding
- National Natural Science Foundation of China [91740117, 81630017, 81770546, 81700479]
- National Key R&D Program of China [2018YFC1705400]
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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.
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