树突状细胞(DCs)的活化在启动银屑病早期炎症反应中发挥着重要的作用，但其机制不清。我们的预实验发现，受体相互作用蛋白激酶3(RIPK3)在银屑病和咪喹莫特鼠模型皮损中均升高，沉默RIPK3可下调LL-37的表达，而后者可促进DCs的活化，但RIPK3在DCs活化及银屑病炎性反应中的作用不清。我们认为，RIPK3可通过调控DCs的活化来启动银屑病早期炎性反应。本项目拟：1.在银屑病皮损中验证RIPK3的过表达及其与LL-37的关系；2.在共培养细胞模型中干扰RIPK3后，检测其对DC、T细胞活化分化及炎症因子的影响；3.在鼠模型和M5细胞模型中抑制或过表达RIPK3后，检测其对上述细胞及炎症因子的作用；4.探讨RIPK3与线粒体自噬的关系，阐明其在上述细胞及因子中具体的作用路径。本项目不仅揭示RIPK3在启动银屑病炎症反应中的作用及其分子机制,也为银屑病的早期治疗提供新靶点和理论依据。

The activation of dendritic cells (DCs) plays an important role in the initiation of the early inflammatory response in psoriasis, while the mechanism is unclear. Our preliminary experiments revealed that the expression of receptor-interacting protein kinase 3 (RIPK3) was elevated in the lesions of both psoriasis and IMQ mice models, and silencing RIPK3 could down-regulate the expression of LL-37, which could promote the activation of DCs. However, the role of RIPK3 in the activation of DCs and the inflammatory response in psoriasis are unclear. We hypothesize that RIPK3 initiates the early inflammatory response in psoriasis by regulating the activation of DCs. This project is intended to: 1. Verify the overexpression of RIPK3 and its relationship with LL-37 in the lesions of psoriatic patients; 2. Interfere with the expression of RIPK3 in the co-cultured cell models, and then detect the effects of activation and differentiation of DCs and T cells and release of inflammatory factors; 3. Inhibit or over-express RIPK3 in mice models and M5 cell models, and then detect the effects of the above cells and the inflammatory factors; 4. To explore the relationship between RIPK3 and mitochondrial autophagy, and to elucidate the specific mechanism in the above cells and inflammatory factors. This project will not only reveal the roles of RIPK3 in initiating the inflammatory response of psoriasis and its molecular mechanism, but also provide a new target and theoretical basis for the early treatment of psoriasis.