长链非编码RNA-AI451557在移植排斥中对T细胞的调控作用及其机制研究

项目名称： 长链非编码RNA-AI451557在移植排斥中对T细胞的调控作用及其机制研究

项目编号： No.81471583

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭志勇

作者单位： 中山大学

项目金额： 71万元

中文摘要： 器官移植排斥反应主要由T细胞介导。长链非编码RNA（lncRNA）对T细胞起重要调控作用。因此，我们假设某些lncRNA能通过调控T细胞影响排斥反应的发生和发展。通过lncRNA芯片和RT- PCR检测，本课题组发现、鉴定lncRNA-AI451557表平在小鼠心脏移植排斥反应中显著上调，并随排斥反应和混合淋巴细胞反应的进展而逐渐升高，且该lncRNA在人和小鼠T细胞中均高表达，以上结果初步验证了我们的假设。本课题拟在体外实验中探讨该lncRNA对T细胞的分化、增殖和功能的调控作用，并明确其作用于T细胞的靶基因及具体分子机制；在小鼠心脏移植模型中，研究下调该lncRNA的表达对T细胞分化、功能及移植排斥反应的作用；最后，在移植患者中探讨该lncRNA用于诊断与预测临床排斥反应的可行性。本项目的开展有可能提出移植免疫排斥反应的新机制，为发现新型药物治疗靶点提供科学依据。

中文关键词： 长链非编码RNA；移植排斥反应；T细胞

英文摘要： Organ transplant rejection is mainly mediated by T cells. Long non-coding RNA (lncRNA) plays an important role in T-cell activation, proliferation and differentiation.We hypothesize that some lncRNAs are involved in the pathogenesis of allograft rejection. Our preliminary experiments using microarray and RT-PCR techniques demonstrated that lncRNA-AI451557 expression was significantly up-regulated in rejecting heart allografts and graft infiltrating lymphocytes, and increased over time during rejection and mixed lymphocytes reactions. Besides, it can be highly expressed in both murine and human T cells. Therefore, these results were in line with our hypothesis. In the current study, we aim to investigate the expression dynamics of lncRNA-AI451557 in immune cells during heart transplantation,test how this lncRNA regulates activation,proliferation and function of CD4+T cells in vitro, predict and verify the target genes and exploit the underlining molecular mechanism, in vivo detect the role of lncRNA-AI451557 in regulating T cells and transplant rejection, and finally exploit the potential of the lncRNA expression as a biomarker in the diagnosis and prediction of rejection in transplant recipients. The project will clarify the regulation of T cells by lncRNA-AI451557 during transplant rejection and may provide a novel therapeutic target for the treatment of immune rejection in clinics.

英文关键词： long non-coding RNA;allograft rejection;T cells