Multiple sclerosis is an autoimmune, neurodegenerative disease, affecting mostly young adults and resulting in progressive disability. It is a multifactorial disorder, with important involvement of both cellular and epigenetic components. Among the epigenetic factors, microRNAs are currently intensively investigated in the context of multiple sclerosis. It has been shown that their biogenesis and function may be regulated by various cytokines. IL-17, a hallmark cytokine of Th17 cells, has been thought to function predominantly as a pro-inflammatory factor, leading to increased disease symptoms. However, there are several studies indicating its protective role during inflammatory process. In this work, we have assessed the impact of high-dose IL-17 administration on microRNAs' expression profile during the preclinical stage of EAE. For selected microRNA, we have performed computational analysis of its potential target mRNAs and cellular pathways. Based on results obtained from in silico analysis, we have chosen genes from neurotrophin signaling pathway for further experiments-BDNF, HRAS, and BCL2. Results obtained in this study suggested that high dose of IL-17 exerts protective activity via miR-155-5p downregulation. Increased expression of all studied genes, especially BCL2, indicated a potential anti-apoptotic function of IL-17 during the preclinical phase of EAE.
Keywords: Bcl-2; Experimental autoimmune encephalomyelitis; Interleukin-17; Multiple sclerosis; microRNAs.