Blimp-1对小鼠allo-HSCT后GVHD发病的调控作用和机制研究

项目名称： Blimp-1对小鼠allo-HSCT后GVHD发病的调控作用和机制研究

项目编号： No.81471580

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： 陈翀

作者单位： 徐州医科大学

项目金额： 71万元

中文摘要： 移植物抗宿主病（GVHD）是T细胞介导的异基因造血干细胞移植后主要并发症，目前对其防治策略仍有较大局限性，因此很有必要深入探索其发病的分子机制。Blimp-1是T细胞增殖分化的重要调控因子，但对其机制所知有限。目前Blimp-1在移植免疫中的作用罕有报道。我们课题组发现，敲除供鼠T细胞Blimp-1基因可减轻受鼠GVHD，在此基础上，我们提出Blimp-1是GVHD的新调控因子。本研究拟通过常规和T细胞特异性Blimp-1缺陷供鼠建立GVHD模型探索Blimp-1对GVHD的调控作用和对HSCT后T细胞增殖活化的影响；并进一步从转录调控和蛋白组学水平解析Blimp-1调控T细胞活化过程的深层机制。本课题的如期完成有望进一步加深对GVHD发病机理的认识，拓宽GVHD防治的思路。

中文关键词： 异基因造血干细胞移植；T细胞；移植免疫；B淋巴细胞诱导成熟蛋白-1；移植物抗宿主病

英文摘要： Graft-versus-host disease is the most sever complication of allo-genetic hematopoietic stem cells transplantation (HSCT), which is considered to be induced by donor T cells. Although current means to prevent and treatment of GVHD is clinical effective, GVHD is still the major obstacle in clinical HSCT.So,it is necessary to further explore the molecular mechanisms of GVHD pathogenesis. Blimp-1 is an important regulatory factor to the proliferation and differentiation of T cells, however, the mechanism of Blimp-1 in reguating T cell proliferation and differentiation is not defined. Until now, little is known anbot the role of Blimp-1 in transplantation immunity. In our previous study, we found that disrupt Blimp-1 gene in donor mice T cells could attenuate GVHD, suggesting that Blimp-1 was a novel regulatory factor of GVHD. In this study, we will use donor mice with T cell specific Blimp-1 defeciency and wide type mice to set GVHD models. The regulatory role and effect of Blimp-1 on T cell activation and proliferation in GVHD mice will be explored. Furthermore, the mechanism of Blimp-1 in T cell activation will be studied in transcriptional control and proteomics aspects respectively. If succeed, it will be helpful to further elucidate the mechanism of GVHD pathogenesis, and will provide new strategies for prevention and treatment of GVHD.

英文关键词： allo-HSCT;T cells;Transplantation Immunology;Blimp-1;GVHD