CD100调控角质形成细胞糖酵解代谢在银屑病发病中的作用及机制研究

银屑病是一种慢性炎症性皮肤病，角质形成细胞（KC）活跃的糖酵解代谢与其炎症进展密切相关，但机制不清。研究表明，免疫调节分子CD100及其受体Plexin-B2在银屑病患者表皮KC中高表达。我们发现，CD100/Plexin-B2促进KC糖酵解代谢，而代谢终产物乳酸可促进NLRP3炎症小体活化和促炎细胞因子的分泌。以上结果提示：银屑病表皮KC高表达的CD100/Plexin-B2促进KC糖酵解代谢终产物乳酸产生，进而促进NLRP3炎症小体活化参与银屑病炎症反应。本项目拟首先在临床样本和银屑病小鼠模型中明确糖酵解代谢与CD100及银屑病发病的关系；进一步在细胞水平阐明CD100调控KC糖酵解代谢参与银屑病炎症的具体机制；最后在小鼠模型中确认干预CD100对KC糖酵解代谢和银屑病样损害发生的影响。旨在揭示KC糖酵解代谢参与银屑病炎症的具体分子机制，为银屑病治疗提供新的策略和关键靶点。

Psoriasis is a chronic inflammatory skin disease, the active of keratinocyte (KC) glycolysis, which is closely related to its inflammatory progress, but the causal mechanism is still unclear. The studies have shown that immunoregulatary molecules, CD100 and its receptor of Plexin-B2 were highly expressed in psoriatic lesion. We previously found that CD100/Plexin-B2 significantly promoted KC glycolysis in vitro; meanwhile, lactate, the product of glycolysis could effectively promote KC NLRP3 inflammasome activation and the release of the pro-inflammatory cytokines. Therefore, we put forward the hypothesis that CD100/Plexin-B2 promoted KC glycolysis, which is involved in inflammatory response of psoriasis. We will firstly confirm that glycolysis is implicated in the development of psoriasis in clinical samples and IMQ-induced psoriasis-like mouse model, and then explore the underlying mechanism of CD100 in regulating glycolysis involved in inflammatory response of psoriasis, and finally to verify the effect of CD100 on KC glycolysis and psoriasis inflammatory response in IMQ psoriasis-like dermatitis model. This study will illustrate the specific mechanism of CD100 regulating KC glycolysis on psoriasis inflammatory response, which may help to develop new therapeutic treatments for psoriasis.