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

Abstract

BackgroundOne 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.ObjectivesWe 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 MethodsForty 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-β, mTOR and JAK/STAT.ResultsWe 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.ConclusionsAccording 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.

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

“…To our knowledge none of the miRNAs identified in this study had been previously defined to play a role in Tregs. However, miR-141 and Treg numbers were shown to fluctuate in relapsing and remitting phases of multiple sclerosis (Naghavian et al, 2015). In addition, miRNAs, such has miR-155, which regulate normal Treg development and function (Lu et al, 2009;Gao et al, 2012;Josefowicz et al, 2012;Dooley et al, 2013;Kohlhaas et al, 2009), were not found to be altered in the naïve CD4 T cells of patients with multiple sclerosis (Guerau-de-Arellano et al, 2011).…”

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

“…Some number of miRNA have been reported to modulate immune processes. Mir-26a-5p, mir-140-3p and mir-339-5p, for example, can inhibit NF-κB expression [42–44]; and mir-185-5p and mir-200a-3p can regulate immune cell proliferation and differentiation [45, 46]. While to role of miRNAs has largely been studies in cells, miRNAs can also readily be found in the blood.…”

MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB

“…Efforts have been made in haematopoietic differentiation studies. MIR141 and MIR200A were identified as potential important miRNAs in the progression of multiple sclerosis through inducing differentiation of Th17 cells and inhibiting differentiation to Treg cells (Naghavian et al, 2015). MIR200B-3p regulates monocyte/macrophage differentiation by targeting p38IP (Yu et al, 2016).…”