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

• DOI: 10.1096/fj.201901446r
• Publication Date: 2019-10-24T01:35:41Z
• Authors: Yankai Wei; Sisi Chen; Deming Sun; Xue Li; Ruihua Wei; Xiaorong Li; Hong Nian
• Keywords: 0301 basic medicine; Biochemistry & Molecular Biology; Physiology; Medical Physiology; Inbred C57BL; Autoimmune Disease; Autoimmune Diseases; Uveitis; Mice; 03 medical and health sciences; IL-23; Medical physiology; Receptors; IL-22; 2.1 Biological and endogenous factors; Animals; Aetiology; Eye Disease and Disorders of Vision; Biomedical and Clinical Sciences; Animal; Forkhead Box Protein O3; pathogenic Th17 cells; GM-CSF; Receptors, Interleukin; Biological Sciences; Interleukin; Up-Regulation; Mice, Inbred C57BL; Disease Models, Animal; MicroRNAs; Gene Expression Regulation; Biochemistry and cell biology; Disease Models; Th17 Cells; Female; Biochemistry and Cell Biology; IL-23R; Biotechnology; Signal Transduction

Pathogenic T helper (Th)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 Th17 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 Th17 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 Th17 cell responses partially via suppression of IL‐23 receptor expression. Thus, our results reveal an important role for miR‐223‐3p in autoreactive Th17 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 Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression. FASEB J. 33, 13951‐13965 (2019). www.fasebj.org