Role of Galphaq in pathogenesis of psoriasis, a new mechanism about the immune regulation in psoriasis

Abstract

Psoriasis (PSO) is a chronic inflammatory skin disease characterized with skin lesions and abnormal keratinocyte proliferation. The immune dysregulation is involved in the pathogenesis of PSO. However, the detail of immune regulation in PSO is still not very clear. Gαq, the alpha subunit of the Gq protein, played important role in the immune regulation. In this study, we aimed to investigate whether Gαq was involved in the pathogenesis of PSO. We detected the Gαq expression level and analyzed its relationship with test parameters of PSO patients. Furthermore, we used imiquimod to induce PSO mouse model in Gnaq -/- bone marrow (BM) chimeric mice. The inflammatory cytokines and its correlation with Gαq expression were analyzed both in PSO patients and mice. The results showed that the Gαq expression in PSO patients was much lower and negatively correlated with PSO Area and Severity Index (PASI), CRP, cholesterol and low-density lipoprotein. In PSO mice models, the skin lesion and keratinocyte proliferation were much more serious in Gnaq -/- BM chimeric mice. Also, the proportions of Th17 cells in Gnaq -/- BM chimeric mice were much higher than WT mice. Furthermore, the IL-17A and TNF-α in Gnaq -/- chimeric mice were also higher. Moreover, IL-17A and TNF-α in PSO patients were negatively associated with the Gαq expression. Our results indicated that Gαq was involved in the pathogenesis of PSO, and its regulation on Th17 cell differentiation and cytokine production might contribute to part of the mechanism of immune dysfunction of PSO.

Keywords: Gαq; Immune regulation; Inflammation; PSO; Th17 cell.