Renin Promotes STAT4 Phosphorylation to Induce IL-17 Production in Keratinocytes of Oral Lichen Planus

• Main Authors: Xuejun Ge, Hanting Xie, Tivoli Nguyen, Bin Zhao, Jing Xu, Jie Du
• Format: Article
• Language: English
• Published: Elsevier 2020-04-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S258900422030167X

Summary: Interleukin-17 (IL-17) is highly expressed in the epithelial layer of oral lichen planus (OLP), but the underlying mechanism for IL-17 overexpression remains unknown. Here, we identify renin that is induced by NF-κB pathway contributes to the increase of IL-17 in human oral keratinocytes (HOKs). We describe that the release of cellular renin leads to the phosphorylation of Janus kinase 2 (JAK2) protein. The phosphorylated JAK2 recruits and activates the signal transducer and activator of transcription 4 (STAT4) by phosphorylating STAT4's tyrosine residue 693 (Tyr693). The now-activated STAT4 translocates into nucleus and binds to the promoter region of IL-17 gene in HOKs. Genetic interference of renin restores IL-17 levels in OLP cell models. Collectively, our results reveal that renin upregulates IL-17 expression by enhancing STAT4 phosphorylation. This discovery unveils an underpinning by which IL-17 is increased in oral keratinocytes and provides potential targeted therapies for OLP patients. : Oral Medicine; Molecular Biology; Immunology Subject Areas: Oral Medicine, Molecular Biology, Immunology