miR-1246 inhibits NFATc1 phosphorylation and regulates Th17 cell activation in the pathogenesis of severe alopecia areata

다국어 초록 (Multilingual Abstract)

Background: We found microRNA (miR)-1246 to be significantly differentially expressedbetween severe active alopecia areata (AA) patients and healthy individuals.
Objective: To explore the role and mechanism of miR-1246 in severe AA.
Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ Tcells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistryassays. Peripheral CD4+ T cells from the AA patients were transfectedwith lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis wereused to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclearreceptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylatedNFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA wasused to measure cytokine levels.
Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantlyincreased 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 cellsbut not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltratinginflammatory 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 theCD4+IL-17+ cells proportion and the IL-17F level.
Conclusion: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may bebeneficial in the severe AA treatment.

참고문헌 (Reference)

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