miR-182-5p inhibits the pathogenic Th17 response in experimental autoimmune uveitis mice via suppressing TAF15.

Linshen Zhang, Peng Sun, Yu Zhang, Ya Xu, Yi Sun

Biochemical and biophysical research communications 2020 Aug 27

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CD4+ T helper 17 (Th17) cells play a contributory role in uveitis and other autoimmune disorders. However, less is understood about the contribution of microRNAs (miRNAs) in regulating the pathogenic Th17 response in uveitis. The in vivo experimental autoimmune uveitis (EAU) model was constructed in female C57BL/6 mice. Primary EAU mouse CD4+ T-cells and the murine T-cell line EL4 were used for in vitro experiments. miRNA mimic/inhibitor, lentiviral overexpression plasmids, and small interfering RNAs (siRNAs) were used to modulate miR-182-5p and TAF15 expression. CD4+ T-cells from healthy controls (HC, n = 15), active Behçet's disease with uveitis (BD, n = 15), or active sympathetic ophthalmia with uveitis (SO, n = 15) were analyzed for miR-182-5p, TAF15, and Th17 marker gene expression. miR-182-5p was downregulated in EAU mouse-derived Th17 cells. miR-182-5p negatively regulated Th17 cell development in vitro. miR-182-5p mimic therapy in transplanted Th17 cells ameliorated EAU severity in vivo. Mechanistically, miR-182-5p directly inhibited the transcriptional initiator TATA-binding protein-associated factor 15 (TAF15, TAFII68). miR-182-5p's inhibition of TAF15 negatively regulated Th17 cell development by suppressing STAT3 phosphorylation. TAF15 and Th17 marker expression were positively correlated in CD4+ T-cells from BD and SO patients. miR-182-5p mimic therapy inhibits the pathogenic Th17 response in EAU mice. miR-182-5p's inhibition of TAF15 negatively regulates Th17 cell development by suppressing STAT3 phosphorylation. As TAF15 shows a positive relationship with Th17 cell markers in uveitis patients, the miR-182-5p/TAF15 axis shows promise as a therapeutic target for uveitis. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Linshen Zhang, Peng Sun, Yu Zhang, Ya Xu, Yi Sun. miR-182-5p inhibits the pathogenic Th17 response in experimental autoimmune uveitis mice via suppressing TAF15. Biochemical and biophysical research communications. 2020 Aug 27;529(3):784-792