OPN3 regulates keratinocyte function and modulates psoriasis pathogenesis under pathological conditions

Summary: Abstract Body: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive keratinocyte proliferation, immune cell infiltration, and increased angiogenesis, with an unclear pathogenesis. Opsin3 (OPN3), a member of the G protein-coupled receptor (GPCR) family, plays significant roles beyond its classical functions, including cell proliferation, apoptosis, metabolism, adaptive thermogenesis, tumorigenesis, vasodilation, and immunity. However, the role of OPN3 in psoriasis remains unclear. This study aims to investigate the expression patterns of OPN3 in psoriatic and normal skin and explore its relationship with disease severity. We detected OPN3 expression in psoriatic lesions, perilesional skin, and normal skin using immunohistochemistry (IHC), and constructed a psoriasis mouse model along with cell models with lentiviral-mediated OPN3 knockdown and overexpression to explore the relationship between OPN3 and disease severity. IHC results showed that OPN3 expression was decreased in psoriatic lesions compared to normal skin (p < 0.01). Interestingly, intradermal injection of lentivirus overexpressing OPN3 alleviated skin thickening and vascularization in an imiquimod-induced psoriasis-like dermatitis mouse model (p < 0.01). Furthermore, OPN3 knockdown in keratinocytes reduced cell proliferation (p < 0.01) and increased the protein expression levels of the differentiation marker K10. Our study identifies the critical role of OPN3 in maintaining the balance of keratinocyte proliferation and differentiation and in the pathogenesis of psoriasis, suggesting that OPN3 could be a potential therapeutic target for alleviating psoriasis symptoms. Luo Huanhuan¹, Hongguang Lu¹ 1. Guizhou Medical University, Guiyang, Guizhou, China. Epidermal Structure and Barrier Function