miR-223-3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression
Autor: | Wei, Yankai, Chen, Sisi, Sun, Deming, Li, Xue, Wei, Ruihua, Li, Xiaorong, Nian, Hong |
---|---|
Rok vydání: | 2019 |
Předmět: |
Biochemistry & Molecular Biology
Animal Physiology Forkhead Box Protein O3 Medical Physiology GM-CSF pathogenic Th17 cells Interleukin Inbred C57BL Autoimmune Diseases Up-Regulation Uveitis Mice MicroRNAs Gene Expression Regulation IL-23 Disease Models Receptors IL-22 Animals Th17 Cells Female Biochemistry and Cell Biology IL-23R Signal Transduction |
Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol 33, iss 12 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |