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

Immunohorizons. 2020 Jun 9;4(6):308-318. doi: 10.4049/immunohorizons.2000008.

Abstract

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Differentiation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • MicroRNAs / metabolism
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / immunology*
  • PTEN Phosphohydrolase / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • MicroRNAs
  • Mirn22 microRNA, mouse
  • PTEN Phosphohydrolase
  • Pten protein, mouse