最新研究表明银屑病是一种与代谢异常相关的系统性、复发性、炎症性皮肤病，其中炎性介质IL-1β诱导下的Th17细胞分化和IL-17相关通路是其重要的发病机制。高尿酸血症是常见的代谢异常状态，临床研究发现其与银屑病的发病和严重程度显著相关，但尚缺乏二者之间作用机制的研究。尿酸是人体嘌呤代谢的终产物，其晶体可通过TLR4/NLRP3通路激活DC细胞分泌IL-1β，参与多种炎症性疾病的发病过程。尿酸的生物学活性与银屑病的发病机制存在一定重叠，因此本课题基于上述证据，拟联合氧嗪酸钾诱导的小鼠高尿酸血症模型和咪喹莫特诱导的小鼠银屑病模型，探究尿酸是否可通过TLR4/NLRP3/IL-1β信号通路活化真皮DC细胞，进而诱导Th17细胞分化，并最终影响银屑病的发病和疾病进展。揭示尿酸代谢异常在银屑病发病机制中的作用，并最终为银屑病的代谢性预防和治疗提供新的思路和干预靶点。

Psoriasis is currently known as a systemic, recurrent and inflammatory dermatological disease which is considered highly related to metabolism disorders. IL-1β-induced Th17 differentiation and IL-17-related pathways play a crucial role in the pathogenesis of psoriasis. Hyperuricemia is among the most common metabolism abnormalities in patients, and many clinical observations have revealed positive correlations associating the onset or progression of psoriasis and hyperuricemia, however, the exclusive interactive mechanism still remains under-investigated. Being the end product of purine metabolism in human, uric acid is able to activate dendritic cells to release IL-1β via TLR4/NLRP3 signaling, which is the causative factor for many related inflammatory conditions. Notedly, there is a certain overlap in the bioactions of uric acid and the pathogenesis of psoriasis. Therefore, based on evidence listed above, we herein propose a hypothesis that uric acid might influence the development of psoriasis via its actions on TLR4/NLRP3/IL-1β signaling, through which dendritic cells are activated and Th17 cells are polarized. By carrying out this project, we hope to reveal a new metabolic mechanism in the psoriasis onset, and therefore provide further insights and targets for the metabolic prevention and therapy of this disease.