miR-223-3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression

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(h)17 cells in EAU remains largely unknown. Here, we have reported that miR-223-3p was significantly up-regulated in interphotoreceptor retinoid-binding protein specific Th17 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(h)17 cells in a T-cell transfer model of EAU. Mechanistic studies showed that miR-2233-p directly repressed the expression of forkhead box 03 (FOXO3), and FOXO3 negatively regulated pathogenic Th17 cell responses partially via suppression of IL-23 receptor expression. Thus, our results reveal an important role for miR-223-3p in autoreactive T(h)17 cell responses and suggest a potential therapeutic avenue for uveitis.