Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients

Eur J Immunol. 2010 Mar;40(3):888-98. doi: 10.1002/eji.200940032.


MicroRNA (miRNA) are a class of post-transcriptional regulators of gene expression targeting mRNA for translational repression and/or degradation. We analyzed the expression of 365 miRNA in lymphocytes in relapsing-remitting MS patients, and show the first evidence for distinct miRNA expression profiles in CD4(+), CD8(+) and B cells in MS when compared with those in healthy volunteers. MiR-17-5p, which is involved in autoimmunity, was up-regulated in CD4(+) cells from MS patients. This was correlated with alterations in the expression of potential target genes of miR-17-5p, i.e. phosphatase and tensin homology and phosphatidyl-inositol-3-kinase regulatory subunit 1, which were down-regulated upon stimulation of CD4(+) cells with anti-CD3/CD28 in vitro. Functional experiments with a synthetic inhibitor of miR-17 supported the link between miRNA expression and the altered target gene expression. Moreover, we found distinct responses of deregulated miRNA to stimulation, i.e. miR-17-5p and miR-193a were strongly up-regulated, in contrast to the down-regulation of miR-497, miR-1 and miR-126. Other deregulated miRNA did not respond to the stimulation probably due to other, non-T-cell activation related, mechanisms in their mode of action. Our findings support the role of miRNA-dependent regulatory mechanisms in the immunopathogenesis of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / physiology
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Separation
  • Female
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Profiling*
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • MIRN17 microRNA, human
  • MicroRNAs