MiR-۹-۵p and miR-۱۰۶a-۵p dysregulated in CD۴+ T-cells of multiple sclerosis patients and targeted essential factors of T helper۱۷/regulatory T-cells differentiation

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS.Recent evidence indicates that Interleukin ۱۷ (IL-۱۷)-producing T helper cells (Th۱۷ cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th۱۷ and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-۹-۵p and miR-۱۰۶a-۵p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th۱۷ master transcription factor) as direct target of miR-۱۰۶a-۵p and forkhead box P۳ (FOXP۳; Treg master transcription factor) as indirect target of miR-۹-۵p in CD۴+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods:Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in ۴۰ RR-MS patients and ۱۱ healthy individuals. Thus, FOXP۳ and RAR-related orphan receptor γt (RORγt) was assessed in CD۴+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th۱۷/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-۹-۵p and down-regulation of miR-۱۰۶a-۵p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP۳ wereup-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-۹-۵p and miR-۱۰۶a-۵p and their targets suggest a possible inducing role of miR-۹-۵p and suppressing role of miR-۱۰۶a-۵p in differentiation pathway of Th۱۷ cells during MS pathogenesis.

کلیدواژه ها:

MicroRNA ، MiR-۱۰۶a-۵p ، MiR-۹-۵p ، Multiple Sclerosis ، Th۱۷