title: MiR-384 Regulates the Th17/Treg Ratio during Experimental Autoimmune Encephalomyelitis Pathogenesis.
abstract: Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS), during which IL-17-producing CD4+T helper (Th17) cells accumulate in the central nervous system (CNS). In this study, we identified levels of miR-384 as significantly increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Over-expression of miR-384in vivoled to severe EAE, characterized by exacerbated demyelination, and increased inflammatory cell infiltration of the spinal cord; inhibition of miR-384 reversed these changes. Both the percentage of Th17, and ratio of Th17/regulatory T (Treg), cells were elevated in miR-384-transfected EAE mice, which was consistent with the observed upregulation of expression of IL-17 and the Th17 lineage-specific transcription factor, RORγt. Importantly, transfer of miR-384 overexpressing naïve T cells from wild-type (WT) toRag1-/-mice, which are deficient in functional autologous T and B cells, led to aggravated EAE pathogenesis, while an miR-384 inhibited group was protected from EAE. Moreover, miR-384 promoted differentiation of naïve T cells into Th17 cellsin vitro. Furthermore, target prediction and dual luciferase reporter assays demonstrated that suppressor of cytokine signaling 3 (SOCS3), a gene encoding protein with an established role in Th17 differentiation, was a direct target of miR-384. Our results demonstrate an important role for miR-384 in regulation of the Th17/Treg ratio during the pathogenesis of EAE, indicating that this molecule may have potential as a biomarker and/or therapeutic target in MS.
authors.affiliation: Department of Neurobiology, Xuzhou Medical University Xuzhou, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University Xuzhou, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Neurobiology, Xuzhou Medical University Xuzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Xuzhou Medical University Xuzhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Xuzhou Medical University Xuzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University Xuzhou, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Neurobiology, Xuzhou Medical University Xuzhou, China.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Yao
keywords: SOCS3; Th17/Treg; experimental autoimmune encephalomyelitis; miR-384; multiple sclerosis