MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Jan 15;266(1-2):56-63. doi: 10.1016/j.jneuroim.2013.09.019. Epub 2013 Oct 8.

Abstract

Mammalian noncoding microRNAs (miRNAs) are suggested to be involved in immune system function. We found that miR-155 expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). Knockdown of miR-155 resulted in low Th1 and Th17 cells and mild EAE, and its overexpression led to more Th1 and Th17 cells and severe EAE. MiR-155 promoted the development of inflammatory Th17/Th1 cell subsets. These findings demonstrate that miR-155 confers susceptibility to EAE by affecting inflammatory T cell responses and can be a new target for therapy of multiple sclerosis.

Keywords: Experimental autoimmune encephalomyelitis; MicroRNAs; Multiple sclerosis; Th1 cells; Th17 cells.

MeSH terms

  • Adult
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Spleen / pathology
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism*
  • Th17 Cells / drug effects
  • Th17 Cells / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*

Substances

  • Cytokines
  • Enzyme Inhibitors
  • MIRN155 microRNA, human
  • MicroRNAs