Abstract
SummaryInterleukin-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.
Highlights
Oral lichen planus (OLP) is a chronic relapsing inflammatory disorder affecting the mucous membranes of gums, buccal mucosa, palate, and tongue(Cheng et al, 2016)
Renin Levels Are Upregulated in the Field of OLP Because renin is reported to be involved in autoimmune diseases (He et al, 2019), we collected oral biopsies from patients with OLP and healthy individuals, sampled from clinically lesion and unaffected mucosa, to test renin expression in these tissues
Our immunohistochemistry staining data confirmed the upregulation of renin in OLP and indicated that the overexpressed renin is localized in the cytoplasm of oral keratinocyte rather than in nucleus (Figure 1D)
Summary
Oral lichen planus (OLP) is a chronic relapsing inflammatory disorder affecting the mucous membranes of gums, buccal mucosa, palate, and tongue(Cheng et al, 2016). Numerous studies have suggested that OLP is an autoimmune response-driven disease in a common consensus, the exact pathogenesis remains unclear. Multiple pathogenic factors, such as autoimmune response, mental stress, infection, and hypersensitivity, have been found to contribute to OLP onset (Cheng et al, 2016). Because OLP is refractory in clinic, much attention has been given to symptomatic improvement (Cheng et al, 2016). Explorations regarding the pathogenies of OLP and curative treatments of it are required
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