Regulation of Th17 cell pathogenic function by miR-183/96/182

Th17 cells are key players in autoimmune diseases. However, the roles of non-coding RNAs in Th17 cells are largely unknown. Here, we show that deletion of the Dicer gene specifically in Th17 cells protects from experimental autoimmune encephalomyelitis (EAE). Th17 cells highly express the miR-183/96/182 cluster (miR-183C), in response to IL-6/STAT3 signaling. Moreover, miR-183C regulates pathogenic cytokine expression during Th17 development. Furthermore, transcription factor Foxo1 is one of functional targets of miR-183C in Th17 cells: Foxo1 negatively regulates the pathogenicity of Th17 cells and miR-183C represses Foxo1 expression. Collectively, our results demonstrate one of crucial roles for miR-183C cluster in regulation of Th17 cell function in autoimmune diseases. Overall design: Control vector- or miR-96-overexpressing T cells and miR-183C+/+ or miR-183C-/- T cells were cultured under the Th17(23) condition and were harvested on day 4-5. Cell sorting was performed using a FACSAria cell sorter to obtain GFP-positive cells. Total RNA was extracted using the TRIzol reagent, enriched for polyA-containing RNAs and submitted to RNA-Seq.