ADSC对GATA3/T-Bet的转录调控及其在ITP中的作用机制探讨

项目名称： ADSC对GATA3/T-Bet的转录调控及其在ITP中的作用机制探讨

项目编号： No.81500091

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： 肖建红

作者单位： 南华大学

项目金额： 18万元

中文摘要： 目前认为，ITP的发生发展与机体Th1/Th2细胞因子失衡密切相关。申请者已研究发现，ADSCs可抑制Th1因子分泌，并上调Th2因子，提高ITP小鼠血小板水平。且前期对ADSCs/CD4+T共培养发现，ADSCs可使PHA诱导的CD4+T增殖抑制，促进ITP来源的CD4+T细胞IL-4、IL-10表达并下调IFN-γ、IL-2。但ADSCs对Th1/Th2因子的具体调控机制尚有待进一步阐明？近年研究证实，CD4+T在ITP中分化失衡与GATA3/T-Bet的转录调控密切相关。结合前期工作，本研究继续在共培养体系中观察ADSCs对ITP患者CD4+T的分化影响，检测Th1/Th2因子及GATA-3/T-bet等表达。然后沉默小鼠T细胞GATA-3或和T-bet基因，探究其上下游相关基因及细胞因子变化。进而探明ADSCs对ITP的作用机制，为确立ADSCs作为防治ITP的新靶点提供科学依据。

中文关键词： 免疫性血小板减少性紫癜；CD4+T细胞；脂肪来源的间充质干细胞；GATA3/T-Bet；；免疫调节

英文摘要： It is now generally accepted that the Th1 / Th2 cytokines imbalance resulted from the immunologic disorder of T cells play a key role in ITP. Our previous study found that ADSCs could inhibit Th1 cytokine secretion and increase the Th2 cytokines level, and improve the level of platelet in ITP mice. And the applicant found that ADSCs could inhibit the proliferationion of T cell induced by PHA, and promoting the expression of IL–10 and IL - 4 in T cells of ITP paitents reducing IFN-γ and IL - 2 by ADSCs/T cells co-culture. However, it is not clear the specific regulation mechanism of Th1 / Th2 cytokines after ADSCs took part in? especially for Th cell differentiation regulation, all the questions were still to be resolved. In recent years, it confirmed that the differentiation imbalances of CD4 + T in ITP are closely related with GATA3 / T - Bet transcription regulation. Combined with previous work, in this study we would observe the Th1/Th2 differentiation in the ADSCs/CD4+ T co-culture system by detecting Th1 / Th2 factors and GATA - 3 / T - bet, etc. Then to silence GATA - 3 or and T - bet genes in the T cells of mice, and detect its upstream and downstream related genes and cytokines. Finally clarify its mechanism and ensure the ADSCs as new targets to control ITP.

英文关键词： immune thrombocytopenia;CD4+T cells;Adiposed-derived stem cells;GATA3/T-Bet ;immune regulation