GSE134895
The microRNA miR-22 represses T helper 17 cell pathogenicity by targeting PTEN-regulated pathways
Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. Here, we dissected the role of miR-22 in pathogenic Th17 cells by autoantigen-specific disease models. We first showed that miR-22 was upregulated in peripheral lymphoid organs and spinal cords of mice developed autoimmune encephalomyelitis. Although miR-22 was upregulated in multiple helper T cell subsets, it was dispensable for T helper cell differentiation in vitro. While miR-22-/- mice exhibited milder symptoms of disease in an active EAE model, adoptive transfer of miR-22-/- 2D2 Th17 cells into naive recipient mice promoted higher disease incidence and severity compared to mice transferred with control 2D2 Th17 cells. Global transcriptional analysis of miR-22-deficient pathogenic Th17 cells revealed upregulated genes in phosphatase and tensin homologue (PTEN)-mediated pathways, and Pten was further identified as one of its potential targets. Therefore, we identified that Th17 cell intrinsic-miR-22 could protect mice from autoimmunity by targeting PTEN-regulated pathways. Overall design: RNA-seq for Mir-22 wild-type and knock-out in Th17 (23) cells with 3 replicates.