The MicroRNA-183-96-182 Cluster Promotes T Helper 17 Cell Pathogenicity by Negatively Regulating Transcription Factor Foxo1 Expression.
Animals; Cells, Cultured; DEAD-box RNA Helicases; Encephalomyelitis, Autoimmune, Experimental; Forkhead Box Protein O1; Humans; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Multiple Sclerosis; Receptors, Interleukin-1 Type I; Ribonuclease III; STAT3 Transcription Factor; Th17 Cells
T helper 17 (Th17) cells are key players in autoimmune diseases. However, the roles of non-coding RNAs in Th17 cell development and function are largely unknown. We found that deletion of the endoribonuclease-encoding Dicer1 specifically in Th17 cells protected mice from experimental autoimmune encephalomyelitis. We found that the Dicer1-regulated microRNA (miR)-183-96-182 cluster (miR-183C) was highly expressed in Th17 cells and was induced by cytokine IL-6-STAT3 signaling. miR-183C expression enhanced pathogenic cytokine production from Th17 cells during their development and promoted autoimmunity. Mechanistically, miR-183C in Th17 cells directly repressed expression of the transcription factor Foxo1. Foxo1 negatively regulated the pathogenicity of Th17 cells in part by inhibiting expression of cytokine receptor IL-1R1. These findings indicate that the miR-183C drives Th17 pathogenicity in autoimmune diseases via inhibition of Foxo1 and present promising therapeutic targets.
Ichiyama, K., Gonzalez-Martin, A., Kim, B., Jin, H., Jin, W., Xu, W., Sabouri-Ghomi, M., Xu, S., Zheng, P., Xiao, C., & Dong, C. (2016). The MicroRNA-183-96-182 Cluster Promotes T Helper 17 Cell Pathogenicity by Negatively Regulating Transcription Factor Foxo1 Expression.. Immunity, 44 (6). http://dx.doi.org/10.1016/j.immuni.2016.05.015