MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata |
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Authors: | Si-si Qi Ying Miao You-yu Sheng Rui-ming Hu Jun Zhao Qin-ping Yang |
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Affiliation: | Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China. |
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Abstract: | BackgroundWe found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals.ObjectiveTo explore the role and mechanism of miR-1246 in severe AA.MethodsExpression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA was used to measure cytokine levels.ResultsmiR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+IL-17+ cells proportion and the IL-17F level.ConclusionmiR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment. |
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