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.
Highlights
Multiple Sclerosis (MS) is a neurodegenerative chronic autoimmune disease of the CNS in which myelin and axons are destroyed to different degrees [1]
Our data suggest that these miRNAs may probably inhibit negative regulators of Th17 cell differentiation, promoting its differentiation
MS is known to be a multifactorial disease with still no definite cause but it appears that combination of environmental factors, epigenetic and genetics lead to continuing immune attacks on the CNS [3]
Summary
Multiple Sclerosis (MS) is a neurodegenerative chronic autoimmune disease of the CNS in which myelin and axons are destroyed to different degrees [1]. MS is known to be a multifactorial disease with still no definite cause but it appears that combination of environmental factors, epigenetic and genetics lead to continuing immune attacks on the CNS [3]. Activation of different STAT transcription factors along with master regulator of each lineage leads to differentiation of various CD4+ T cell subtypes. Following the activation of specific transcription factors of STAT3/RORγt, naïve CD4+ T cells differentiate to Th17 [7,8]. As well as other autoimmune diseases, MS is closely related to deficiencies in immune regulation through malfunction or decreased number of regulatory T cells (Treg) [4] and its differentiation occurs through activation of STAT5/ FOXP3 [8]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
