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

作者：Lindberg Raija L P^*; Hoffmann Francine; Mehling Matthias; Kuhle Jens; Kappos Ludwig

来源：European Journal of Immunology, 2010, 40(3): 888-898.

DOI：10.1002/eji.200940032

• Autoimmune disease
• Expression
• Lymphocytes
• MicroRNA
• MS

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 auto-immunity, 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.

• 出版日期2010-3