MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis

Nat Immunol. 2009 Dec;10(12):1252-9. doi: 10.1038/ni.1798. Epub 2009 Oct 18.


Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate T(H)-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a T(H)-17 cell-associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer T(H)-17 cells and mild EAE, and its overexpression led to more T(H)-17 cells and severe EAE. We also found that miR-326 promoted T(H)-17 differentiation by targeting Ets-1, a negative regulator of T(H)-17 differentiation. Our data show a critical role for microRNA in T(H)-17 differentiation and the pathogenesis of multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Cell Differentiation*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Humans
  • Interleukin-17 / immunology
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Up-Regulation


  • Ets1 protein, mouse
  • Interleukin-17
  • MIRN326 microRNA, human
  • MIRN326 microRNA, mouse
  • MicroRNAs
  • Proto-Oncogene Protein c-ets-1