地西他滨诱导人调节性gammadeltaT细胞Foxp3基因表达上调的分子机制研究

项目名称： 地西他滨诱导人调节性gammadeltaT细胞Foxp3基因表达上调的分子机制研究

项目编号： No.81500157

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： 崔衢

作者单位： 首都医科大学

项目金额： 18万元

中文摘要： 采用现有临床适用药物干预自身免疫性疾病和移植免疫具有广阔的前景。课题前期研究建立了临床用DNA去甲基化药物地西他滨活化人调节性gammadeltaT细胞的方案，通过动物实验证实其免疫抑制活性。地西他滨诱导活化的这群调节性T细胞内Foxp3表达上调，相关分子机制尚不清楚。前期研究结果表明T细胞内转录因子NFAT依赖性信号通路与Foxp3表达密切相关。本研究拟在已有研究基础上，通过体外活化人外周血来源的调节性gammadeltaT细胞，采用流式细胞技术、RT-PCR、甲基化基因芯片和免疫共沉淀等技术，检测调节性T细胞中NFAT信号通路相关分子表达水平，从基因、蛋白质和分子表型等多层面探索NFAT介导的地西他滨诱导人调节性T细胞Foxp3表达的分子机制。本研究将为应用临床适用药物地西他滨介导进行免疫调节奠定理论基础和提供实验依据，通过发掘现有临床药物新的适应症，丰富自身免疫调节治疗的临床策略。

中文关键词： 地西他滨；免疫调节；分子机制

英文摘要： Application of clinically available drugs to treatment of autoimmune diseases and transplation has brilliant perspectives. In a previous study, we established a valid experimental system by using DNA-demethylation agent decitabine to activate human regulatory gammadelta T cells, revealing the immunoregulatory features of decitabine. There are NFAT-dependent and independent pathways involved in Foxp3 up-regulation. However, the molecular mechanisms by which decitaine regulates activation of human regulatory T cells are largely unknown. In this research, based on previous results, we would investigate the expression of NFAT-pathway related molecules by RT-PCR, flow cytometry, gene chip and co-immnoprecipitation, to clarify the molecular mechanisms regulating decitabine-induced regulatory T cell activation. Through this research, we would provide theoretical basis and experimental evidence for decitabine-based immunoregulatory therapy, to explore new application of clinically available drugs and enrich therapeutical intervention strategies for autoimmune diseases and transplantation.

英文关键词： Decitabine;Immune regulation;Molecular mechanisms