title: Linc-MAF-4 regulates Th1/Th2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF.
abstract: In this study, we strove to substantiate the ability of linc-MAF-4 to act as a regulator of pathogenesis during multiple sclerosis (MS). We recruited 34 patients who were diagnosed with MS according to the revised McDonald criteria. Six patients with MS and 5 healthy volunteers contributed peripheral blood mononuclear cells for microarray analysis. Subsequent knockdown and overexpression of linc-MAF-4 in naive CD4+T cells from the additional 28 patients with MS was performed to track changes in CD4+T-cell subsets and their function, as well as to confirm results from the prior microarray analysis. Expression of linc-MAF-4 increased significantly in peripheral blood mononuclear cells of patients with MS compared with those of control participants. In addition, linc-MAF-4 regulated encephalitogenic T helper (Th)1-cell differentiation in patients with MS. Transfection of synthetic linc-MAF-4 into naive CD4+T cells facilitated Th1-cell differentiation and inhibited Th2-cell differentiation by directly inhibiting MAF, which is a Th2-cell transcription factor. Linc-MAF-4 also promoted activation of CD4+T cells from patients with MS. Expression level of linc-MAF-4 correlated with the annual relapse rate in patients with MS. Our results suggest that linc-MAF-4 is involved in the pathogenesis of MS, specifically via regulation of encephalitogenic T cells.-Zhang, F., Liu, G., Wei, C., Gao, C., Hao, J. Linc-MAF-4 regulates Th1/Th2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; and.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; and.
authors.forename: Changjuan
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; and.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; and hjw@tmu.edu.cn.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000293:Adolescent; D000328:Adult; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D062085:RNA, Long Noncoding
keywords: CD4+ T cell; autoimmune diseases; long noncoding RNAs