The MicroRNA miR-22 Represses Th17 Cell Pathogenicity by Targeting PTEN-Regulated Pathways

Li Wang, Rong Qiu, Zhaoyang Zhang, Zhijun Han, Chao Yao, Guojun Hou, Dai Dai, Wenfei Jin, Yuanjia Tang, Xiang Yu, Nan Shen
2020 ImmunoHorizons  
Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. In this study, 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 Th cell subsets, it was dispensable for Th cell differentiation in vitro. Whereas miR-22 -/- mice exhibited milder
more » ... ibited milder symptoms of disease in an active experimental autoimmune encephalomyelitis model, adoptive transfer of miR-22 -/- 2D2 Th17 cells into naive recipient mice promoted higher disease incidence and severity compared with 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.
doi:10.4049/immunohorizons.2000008 pmid:32518131 fatcat:ghcryua6lfhapnmdztmtexnagy