肿瘤坏死因子配体相关分子1A（TL1A）及其受体在寻常型银屑病发病中的作用及机制研究

项目名称： 肿瘤坏死因子配体相关分子1A（TL1A）及其受体在寻常型银屑病发病中的作用及机制研究

项目编号： No.81502719

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李林

作者单位： 成都市第二人民医院

项目金额： 18万元

中文摘要： 本项目基于我们前期重要发现：肿瘤坏死因子样配体1A（TNF-like ligand 1A, TL1A）在寻常型银屑病（psoriasis vulgaris, PV）患者的皮损及血清中表达升高，并且随患者病情的好转而降低；TL1A能够协同IL-23刺激PV患者外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）产生IL-17。因此TL1A可能在银屑病的炎症反应中起到重要作用。拟深入研究：TL1A对人PBMCs促炎症性细胞因子在mRNA及蛋白水平产生的作用、可能依赖的受体和信号通路；阻断TL1A及其受体相互作用对PV小鼠模型的干预作用及机制。本项目从分子、细胞和动物等多个层面来揭示TL1A在PV发病中的作用，扩展我们对TL1A生物学作用的认识，为针对TL1A及其受体靶点治疗PV的新药开发及可能的产业化发展提供坚实的理论依据。未见国内外相关研究。

中文关键词： 肿瘤坏死因子样配体1A；外周血单个核细胞；寻常型银屑病；促炎症性细胞因子

英文摘要： This research is based on our previous findings: TNF-like ligand 1A (TL1A) levels were significantly elevated in both psoriatic skin lesions and serum in patients with psoriasis vulgaris (PV) and the high serum TL1A levels in patients with PV decreased after treatment. Besides, we found that soluble TL1A may synergize with IL-23 to stimulate peripheral blood mononuclear cells (PBMCs) from patients with PV to produce IL-17. So we speculate that TL1A may act as an important mediator of inflammation in PV. In this study, we observe the biologic effects of TL1A in PBMCs. We focus on the effects of TL1A on the production of proinflammatory cytokines at both mRNA and protein levels. Furthermore, we explore the potential contribution of TL1A receptors and signal transduction pathways in TL1A-treated PBMCs and mice. In addition, we also investigate the therapeutic effects of TL1A or its receptors blockade in the animal model of PV. It would be interesting and important to ascertain the effects and mechanisms of TL1A in PV both in vivo and in vitro. It may further extend and deepen the understanding of the biologic effects of TL1A and open new therapeutic opportunities in PV by targeting TL1A and its receptors. No similar study has been found so far.

英文关键词： TNF-like ligand 1A;peripheral blood mononuclear cells;psoriasis vulgaris;proinflammatory cytokines