mTOR信号通路在口腔扁平苔藓T细胞免疫应答中的作用研究

项目名称： mTOR信号通路在口腔扁平苔藓T细胞免疫应答中的作用研究

项目编号： No.81500868

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： 张静

作者单位： 武汉大学

项目金额： 18万元

中文摘要： 口腔扁平苔藓（OLP）是T细胞介导的慢性免疫性炎症疾病，mTOR信号通路可调控抗原提呈、T细胞免疫应答和角质形成细胞的免疫反应。本课题提出OLP中存在着异常的mTOR信号，这种异常表达通过影响T细胞的平衡和免疫功能，参与OLP的发生发展。（1）PCR芯片筛选OLP T细胞差异表达的mTOR通路分子。（2）研究OLP中mTOR通路分子的活化水平及其临床意义。（3）采用RNA干扰技术沉默T细胞上差异表达的mTOR信号分子，观察T细胞的代谢、分化、活化、增殖、凋亡、迁移、自噬情况。（4）研究mTOR信号在T细胞和角质形成细胞交互对话中的作用。（5）探究mTOR通路抑制剂对OLP T细胞免疫功能的调控效应。（6）分析代谢抑制剂对mTOR介导的T细胞免疫功能的调节作用。本课题从T细胞免疫和代谢的全新角度为研究OLP的免疫机制及探索OLP的靶向治疗提供实验依据，具有重要的理论意义和应用价值。

中文关键词： 口腔扁平苔藓；mTOR信号通路；T细胞；免疫；角质形成细胞

英文摘要： Oral lichen planus (OLP) is a chronic T cell-mediated immunity and inflammation disease. Mammalian target of rapamycin (mTOR) plays a key role in antigen presentation, T cell immunity, and immune responses in keratinocyte. Thus, it is speculated that dysregulated mTOR signaling in T cell might involve in OLP through directing T cell homeostatic and functional fates, and in further regulating keratinocyte biology. (1) To detect mTOR signaling in T cell of OLP using PCR arrays, and validate the altered expression of selected genes at mRNA and protein level. (2) To examined the activation level of mTOR signaling in OLP, and to analyze the clinical significance. (3) To silence the altered mTOR signaling via shRNA, and then examine their effects on T cell metabolism, differentiation, activation, proliferation, trafficking, apoptosis and autophagy. (4) To test the role of mTOR signaling in crosstalk between T cell and keratinocyte in OLP. (5) To investigate the effect of mTOR inhibition on OLP T cell immune function. (6) To assay the regulation of metabolic antagonists on T cell immune function mediated by mTOR signaling in OLP. From the perspective of T cell immune and metabolism, this subject potentially reveals an important pathological window for OLP and provides novel strategies for targeted therapeutic intervention of OLP, which not only has high theoretical significance, but also has important practical value.

英文关键词： oral lichen planus;mTOR signaling;T cell;immunity;keratinocyte