免疫检查点蛋白VISTA在Imiquimod 诱导的银屑病样皮肤炎症的作用及机制研究

V-domain Ig Suppressor of T cell Activation (简称VISTA) 是新型免疫检查点，与程序性细胞死亡蛋白PD-1有同源性，在肿瘤免疫治疗及控制自身免疫性疾病中发挥重要作用。银屑病已被定义为器官特异性自身免疫性疾病。我们采用咪喹莫特分别诱导野生型和VISTA ko小鼠产生银屑病样皮肤损伤，VISTA ko 小鼠表现为更严重表皮异常增殖及炎症浸润，表达较高Th17细胞相关因子。针对这一表型，本项目拟采用多色流式技术，固相免疫沉淀，PCR和ELISA等，从整体、细胞、分子水平研究VISTA在银屑病中的机制，揭示VISTA在皮损区不同免疫细胞的表达及对IL-17/IL-22轴炎症级联反应的调节，进一步的，解析VISTA在T细胞受体（TCR）信号通路作用引起T细胞反应及可能的结合靶标蛋白。

V-domain Ig Suppressor of T cell Activation(VISTA) is a novel immune-checkpoint, which is a homolog of PD-1, plays important role in tumor immunotherapy and autoimmune disease. Psoriasis is a chronic inflammatory disease accompanied by keratinocyte hyperproliferation and leukocyte infiltration. To determine whether VISTA regulates psoriasis, we compared skin responses of VISTA ko mice and wide type controls in an imiquimod (IMQ) –induced murine model of psoriasis. VISTA ko mice showed severe epidermal hyperplasia, greater neutrophilic infiltration, and higher expression of Th17 cytokines (versus WT mice). In this project, we will use the flow, immunohistochemistry, ELISA, PCR and western blot techniques to study the mechanism of VISTA in regulation of psoriasiform dermatitis, especially maybe through expression on γδ T cell and induce the IL-17/IL-22 signaling cascade. Furthermore, VISTA suppressed T cell activation by T cell receptor signaling pathway was also studied and to identify the binder of VISTA.