%A Ghorbani,Samira %A Talebi,Farideh %A Chan,Wing Fuk %A Masoumi,Farimah %A Vojgani,Mohammed %A Power,Christopher %A Noorbakhsh,Farshid %D 2017 %J Frontiers in Immunology %C %F %G English %K Experimental autoimmune encephalomyelitis,Multiple Sclerosis,microRNA,MiR-181,SMAD7 %Q %R 10.3389/fimmu.2017.00758 %W %L %M %P %7 %8 2017-July-19 %9 Original Research %+ Farshid Noorbakhsh,Department of Immunology, School of Medicine, Tehran University of Medical Sciences,Iran,f-noorbakhsh@sina.tums.ac.ir %# %! Role of miR-181 in the pathogenesis of autoimmune neuroinflammation %* %< %T MicroRNA-181 Variants Regulate T Cell Phenotype in the Context of Autoimmune Neuroinflammation %U https://www.frontiersin.org/articles/10.3389/fimmu.2017.00758 %V 8 %0 JOURNAL ARTICLE %@ 1664-3224 %X BackgroundRecent studies have revealed that multiple sclerosis (MS) lesions have distinct microRNA (miRNA) expression profiles. miR-181 family members show altered expression in MS tissues although their participation in MS pathogenesis remains uncertain. Herein, we investigated the involvement of miR-181a and miR-181b in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE).MethodsmiR-181a and -b levels were measured in the central nervous system (CNS) of patients with MS and mice with EAE as well as relevant leukocyte cultures by real-time RT-PCR. To examine the role of the miRNAs in leukocyte differentiation and function, miR-181a and -b mimic sequences were transfected into cultured primary macrophages and purified CD4+ T cells which were then analyzed by RT-PCR and flow cytometry. Luciferase reporter assays were performed to investigate the interaction of miR-181a and -b with the 3′-UTR of potential target transcripts, and the expression of target genes was measured in the CNS of EAE mice, activated lymphocytes, and macrophages.ResultsExpression analyses revealed a significant decrease in miR-181a and -b levels in brain white matter from MS patients as well as in spinal cords of EAE mice during the acute and chronic phases of disease. Suppression of miR-181a was observed following antigen-specific or polyclonal activation of lymphocytes as well as in macrophages following LPS treatment. Overexpression of miR-181a and -b mimic sequences reduced proinflammatory gene expression in macrophages and polarization toward M1 phenotype. miR-181a and -b mimic sequences inhibited Th1 generation in CD4+ T cells and miR-181a mimic sequences also promoted Treg differentiation. Luciferase assays revealed Suppressor of mothers against decapentaplegic 7 (Smad7), as a direct target of miR-181a and -b.ConclusionOur data highlight the anti-inflammatory actions of miR-181a and -b in the context of autoimmune neuroinflammation. miR-181a and -b influence differentiation of T helper cell and activation of macrophages, providing potential therapeutic options for controlling inflammation in MS.