银屑病与动脉粥样硬化的关联桥梁—IL-17信号通路及衔接蛋白TRAF3IP2的调控机制

Psoriasis is a chronic inflammatory skin disease with abnormal T lymphocyte infiltration and activation. Among the patients, the incidence of metabolic syndrome and cardiovascular system diseases was significantly higher than that in normal people. Cardiovascular disease is the main cause of death in patients with psoriasis.There is similar immuno-pathological mechanism between psoriasis and atherosclerosis, in which some cytokines play a connecting role. Many studies have shown that IL-23/Th17/IL-17 pathway may play a role in the link between psoriasis and atherosclerosis through excessive inflammatory response mediated by IL-17. TRAF3IP2 is an important adaptin in IL-17 signal transduction process. It can avoid the occurrence of abnormal inflammation through strict control. A number of studies have confirmed that TRAF3IP2 gene is closely associated with the susceptibility to psoriasis, and TRAF3IP2 is an essential factor for a variety of stress factors to lead to vascular endothelial dysfunction and death. From the above, we hypothesized that IL-23/Th17/IL-17 pathway and TRAF3IP2 may act as a connecting bridge and dual control in the occurrence and development of atherosclerosis in psoriasis patients. Based on the above conjecture, we design this subject. We intend to choose human keratinocytes and endothelial cells as the research object and use biology technologies including gene recombination, knockout and transgenic animal to explore the relationship and mechanism of control among IL-23/Th17/L-17 pathway, TRAF3IP2, psoriasis and atherosclerosis. Our results will enrich the pathogenesis of psoriasis with atherosclerosis, provide new possible dual-control therapeutic targets and theoretical basis for developing new drugs for the treatment of psoriasis, improve the quality of life in patients with psoriasis.

银屑病是以T淋巴细胞异常活化为主要特征的慢性炎症性皮肤病，患者中代谢综合征、心血管系统疾病的发生率高于正常人，心血管系统疾病是银屑病患者的主要死因。动脉粥样硬化与冠心病、心肌梗塞关系密切。免疫介导的炎症反应是银屑病与动脉粥样硬化共同的发病机制，二者共享IL-23/Th17细胞/IL-17炎症性通路。TRAF3IP2是IL-17信号通路的衔接蛋白，又介导多种应激因素导致血管内皮细胞死亡，而TRAF3IP2基因是银屑病的重要易感基因。由此推测，IL-17通路可能与TRAF3IP2共同组成联接银屑病与动脉粥样硬化的桥梁，对两种疾病具有双重调控作用。本课题采用基因重组、基因敲除、转基因动物等先进分子生物学技术，体内、外实验探讨IL-17通路、TRAF3IP2关联银屑病与动脉粥样硬化的机制及调控作用,研究结果将提供双重干预治疗的靶点，为研发新型治疗药物提供可能，提高银屑病患者生存质量。