miRNA调控Treg细胞抑制小鼠心脏移植免疫排斥的研究

Searching for a approach which is efficient, low toxicity, inexpensive and durable during controlling the rejection after organ transplantation is still a problem that needs to be solved. Recent studies suggested that miRNAs played an important role in the transplant immune process, perhaps through the way of enhancing the inhibiting ability of Treg cells. Preliminary work of our research group funded by NSFC have already confirmed this idea partly and the resluts of the studies suggested that the important role of miR-146a in regulating Treg cells during the rejection pcocess. On this basis, we plan to filter the differently expressed miRNAs in Treg cells after transplantation through microassy technology. Besides, we will search and prove the target genes of miRNAs using bioinformatics analysis and luciferase reporters. After that, we will establish the mice cardiac tranplantation model using the special mice as the recipient in which the special miRNAs were knocked out in Treg cells with the adoption of cre-loxp system. In addition, we will detect the expression of the target genes and putative surface molecules in Treg cells and further study the change of inhibition function of Treg cells and the key mechanism in different signal pathways to learn the roles of miRNAs in regulating the Treg cells and suppressing the cardiac rejection, and try to find a new way to control the rejection process.

寻找高效、低毒、廉价、作用持久的方法控制器官移植术后免疫排斥仍是尚待解决问题之一。研究显示miRNA参与移植免疫过程，可能增强调节性T细胞抑制免疫排斥的能力。课题组前期工作证实这一猜想，其成果已完成2项国家自然科学基金，证实miR-146a不同表达对Treg细胞及其靶基因的调节作用。在此基础上，本项目拟通过miRNA芯片技术筛选移植术后Treg细胞中差异表达的miRNA，应用生物信息学和荧光报告载体实验验证特异性microRNA的靶基因和相关调控基因，采用cre-loxp系统建立在Treg细胞中特异性敲低或高表达相应miRNA的B6转基因小鼠，构建同种异体心脏移植模型，检测对miRNA靶基因及Treg细胞表面分子表达的影响，观察其对T细胞增殖的抑制功能，并分析相关信号通路关键分子表达。探讨特异性miRNA调控Treg细胞、抑制心脏移植排斥反应的分子机制，建立一种新的抑制移植免疫排斥的方法。

寻找高效、低毒、廉价、作用持久的方法控制器官移植术后免疫排斥仍是尚待解决问题之一。研究显示miRNA参与移植免疫过程，可能增强调节性T细胞抑制免疫排斥的能力。课题组前期工作证实这一猜想，其成果已完成2项国家自然科学基金，证实miR-146a不同表达对Treg细胞及其靶基因的调节作用。在此基础上，本项目拟通过miRNA芯片技术筛选移植术后Treg细胞中差异表达的miRNA，应用生物信息学和荧光报告载体实验验证特异性microRNA的靶基因和相关调控基因，采用cre-loxp系统建立在Treg细胞中特异性敲低或高表达相应miRNA的B6转基因小鼠，构建同种异体心脏移植模型，检测对miRNA靶基因及Treg细胞表面分子表达的影响，观察其对T细胞增殖的抑制功能，并分析相关信号通路关键分子表达。探讨特异性miRNA调控Treg细胞、抑制心脏移植排斥反应的分子机制，建立一种新的抑制移植免疫排斥的方法。