Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients.
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.
Lindberg
Raija L P
RL
Clinical Neuroimmunology, Department of Biomedicine and Neurology, University Hospital Basel, Basel, Switzerland. raija.lindberg@unibas.ch
Hoffmann
Francine
F
Mehling
Matthias
M
Kuhle
Jens
J
Kappos
Ludwig
L
D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C524941:MIRN17 microRNA, human; D035683:MicroRNAs