MiR-1-3p facilitates Th17 differentiation associating with multiple sclerosis via targeting ETS1

L. Li, X. Ma, Y.-F. Zhao, C. Zhang

Department of Neurology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. lilei_lle@163.com

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• Neurology

OBJECTIVE: T helper 17 (Th17) cells are involved in the pathogenesis of multiple sclerosis (MS). The present study aimed to explore the role of miR-1-3p in Th17 cell differentiation associated with MS.

PATIENTS AND METHODS: Expression of miR-1-3p in periphery blood mononuclear cells (PBMC), cerebrospinal fluid (CSF), CD4+ T cells, CD8+ T cells, non-T cells and differentiated CD4+ T cells derived from healthy donors and MS patients during remitted and relapsed stages was detected. Level of ETS1 in PBMC in MS-relapse patients was examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlations among neurofilament light (NF-L), C-reactive protein (CRP), estrogen receptor 1 (ESR), interleukin 17A (IL-17A) in serum, NF-L, C-X-C motif chemokine ligand 13 (CXCL13), chitinase 3 like 1 (CHI3L1), RAR related orphan receptor C (RORC) in CSF, and ETS proto-oncogene 1 (ETS1), RORC in PBMC and miR-1-3p expression were analyzed. The target gene of miR-1-3p was analyzed by performing Dual-Luciferase reporter assay, and the IL-17A+ CD4+ (Th17) cells were detected by flow cytometer. Gene expressions of IL-17A, RORC and Th17 pathogenic were determined by qRT-PCR.

RESULTS: Upregulated miR-1-3p was observed in MS-relapse patients and Th17 cells, and expression of miR-1-3p was positively correlated with MS severity. MiR-1-3p overexpression in naïve CD4+ T cells promoted the differentiation of Th17 cells by upregulating the level of inflammation-associated markers. The expression of ETS1, which was predicted to be the target gene of miR-1-3p, was reduced in PBMC from MS-relapse patients, while the upregulation of ETS1 inhibited the expression of pathogenic genes of Th17.

CONCLUSIONS: The study demonstrated the positive role of miR-1-3p in Th17 differentiation associated with MS via targeting ETS1.

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