银屑病是一种慢性炎症性皮肤病，目前发病机制尚不完全明确。我们的前期研究发现IL-27及其受体在中重度银屑病患者外周血及皮损中的表达显著降低，通过动物模型证实IL-27能显著改善小鼠银屑病样皮损，降低皮损处γδT细胞数量和IL-17A等促炎因子及抗菌蛋白RegIIIγ（REG3A小鼠同源蛋白）的表达，因此我们推测IL-27下调IL-17A-REG3A轴可能是通过调节γδT细胞功能实现的。本研究将在已有研究基础上，以IL-27对银屑病发病过程中的关键炎症细胞γδT细胞的调节功能作为研究切入点，通过体外细胞实验，RNA-seq及蛋白质组学分析，咪喹莫特及IL-23诱导的银屑病小鼠模型以及Il-27r-/-小鼠模型，深入探索IL-27对银屑病γδT细胞及角质形成细胞REG3A表达的调节功能，探究IL-27调节IL-17A-REG3A轴免疫应答在银屑病发病中的作用机制，为临床上靶向治疗提供理论依据。

Psoriasis is a chronic inflammatory skin disease. The pathogenesis of psoriasis still remains unclear. Our previous research revealed that the expression of IL-27 and its receptor was dramatically lower in the serum and lesional skin of psoriasis patients compared to healthy controls, and the epidermal hyperplasia and inflammation induced by imiquimod were decreased with reduced number of γδT cells and decreased production of IL-17A and RegIIIγ (a mouse homolog of human REG3A) in lesional skin after subcutaneous injection of IL-27. So we hypothesize that IL-27 could downregulate IL-17A-REG3A axis via regulating the properties of γδT cells. Thus, we use the mechanism how IL-27 regulates γδT cells as the focus of the study. We plan on investigating the mechanism how IL-27 affects γδT cells and REG3A through in vitro and in vivo experiments, including RNA-seq, proteomics, imiquimod and IL-23 induced psoriasis mouse model as well as Il-27r deficient mice. Our results will also uncover the mechanism how IL-27 downregulates the immune response of IL-17A-REG3A axis and provide a probable novel management of psoriasis by targeting IL-27.