miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis.

ABSTRACT

BACKGROUND: One of the main issues in pathogenesis of MS is Th17/Treg imbalance. There are growing interests in nominating miRNAs involved in Th17 cell differentiation, suggesting them as new therapeutic agents that may reduce progression of different autoimmune diseases specially MS. OBJECTIVES: We assessed transcript levels of miR-141 and miR-200a in MS patients, during relapsing and remitting phases. We also investigated possible role of miR-141, miR-200a in inducing differentiation to Th17 cells. MATERIALS AND METHODS: Forty RR-MS patient samples including relapsing (n=20) and remitting (n=20) phases were chosen. Expression level of miR-141 and miR-200a were measured by RT-q PCR and compared to healthy control group (n=10). In-silico analyses on miR-141 and miR-200a targetome showed involvement of both miRNAs in T helper cell differentiation pathways including TGF-ß, mTOR and JAK/STAT. RESULTS: We observed that percentage of RORγt+ CD4+ T cells increase in relapsing phase while FOXP3+ CD4+ increase in remitting phase of MS patients. Furthermore, both miR-141 and miR-200a show up-regulation in relapsing phase of MS patients compared to remitting and control groups. Interestingly, expression level of target genes of miR-141 and miR-200a, which were assessed through in-silico methods, show down-regulation in relapsing phase of MS patients. CONCLUSIONS: According to our results, miR-141 and miR-200a may be key miRNAs in progression of symptoms of MS through inducing differentiation of Th17 cells and inhibiting differentiation to Treg cells. Our data suggest that these miRNAs may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation.