Malat1 long noncoding RNA regulates inflammation and leukocyte differentiation in experimental autoimmune encephalomyelitis

Published:November 28, 2018DOI:https://doi.org/10.1016/j.jneuroim.2018.11.013

      Highlights

      • Malat1 expression is down-regulated in the CNS of mice during EAE disease.
      • Malat1 expression is reduced in activated macrophages and T cells.
      • Malat1 down-regulation in macrophages augments their differentiation towards the proinflammatory M1 phenotype.
      • Malat1 down-regulation in CD4+ T cells tips the balance of differentiation towards Th1/Th17 and away from - Treg phenotype.
      • Malat1 might be involved in immunopathogenesis of multiple sclerosis through its effects on leukocyte differentiation.

      Abstract

      In this study, we investigated the contributions of the MALAT1 long noncoding RNA to autoimmune neuroinflammation in central nervous system tissues from patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE). Expression of MALAT1 was decreased in the spinal cords of EAE mice as well as in stimulated splenocytes and primary macrophages. MALAT1 downregulation by specific siRNAs enhanced the polarization of macrophages towards the M1 phenotype. Interestingly, siRNA-mediated MALAT1 downregulation shifted the pattern of T-cell differentiation towards a Th1/Th17 cell profile and decreased differentiation towards a Tregs phenotype. Proliferation of T-cells was also increased following MALAT1 downregulation. These data point to a potential anti-inflammatory effect for MALAT1 in the context of autoimmune neuroinflammation.

      Graphical abstract

      Keywords

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