miR-223-3p promotes autoreactive T_h17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting...

Pathogenic T helper (T_h)17 cells are key mediators of autoimmune diseases such as uveitis and its animal model, experimental autoimmune uveitis (EAU). However, the contribution of microRNAs (miRs) to the intrinsic control of pathogenic T_h17 cells in EAU remains largely unknown. Here, we have reported that miR-223-3p was significantly up-regulated in interphotoreceptor retinoid-binding protein-specific T_h17 cells, and its expression was enhanced by IL-23-signal transducer and activator of transcription 3 signaling. Knockdown of miR-223-3p decreased the pathogenicity of T_h17 cells in a T-cell transfer model of EAU. Mechanistic studies showed that miR-223-3p directly repressed the expression of forkhead box O3 (FOXO3), and FOXO3 negatively regulated pathogenic T_h17 cell responses partially via suppression of IL-23 receptor expression. Thus, our results reveal an important role for miR-223-3p in autoreactive T_h17 cell responses and suggest a potential therapeutic avenue for uveitis.-Wei, Y., Chen, S., Sun, D., Li, X., Wei, R., Li, X., Nian, H. miR-223-3p promotes autoreactive T_h17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression.