TRIM38介导的接头蛋白MITA 泛素化调控妊娠母胎识别与耐受机制研究

TRIM38是近年发现的具有典型TRIM蛋白家族保守结构域的蛋白。本研究组通过预实验发现TRIM38介导的MITA泛素化在体外和体内能有效地调控巨噬细胞的活化状态，但具体机制未见报道，此项目拟通过本室已建立的小鼠正常妊娠、自发性流产模型、老年妊娠模型，采用RT-PCR、western blot、启动子分析、染色质免疫共沉淀以及过表达、RNA干涉等方法，分析TRIM38在小鼠妊娠期间母胎界面的动态变化，探讨TRIM38及MITA泛素化水平对巨噬细胞和T细胞分化影响，分析TRIM38介导的MITA的泛素化是如何调控母-胎界面浸润的巨噬细胞IRF3/4/5基因的表达，进而影响母胎界面Thl细胞/Thl7细胞的生成，并利用TRIM38基因敲除小鼠研究TRIM38在母胎界面耐受维持过程中的功能。通过本项目研究有助于阐明TRIM38参与妊娠母胎识别与耐受的机制，为母胎识别与耐受的调控研究增加理论依据。

TRIM38 is a newly found protein belonged to typical TRIM protein family with conserve domain . we previously found that TRIM38 mediated adaptor protein MITA played a role in regulating Toll mediated maternal-fetal immune tolerance, but exact mechanism is unclear. We established normal pregnancy, recurrent abortion animal model, and by RT-PCR，western blot，co-immunoprepitation to analyse TRIM 38 change in maternal-fetal change and related mechanism of ubiquitinating of TRIM38 mediated adaptor protein MITA in regulating Toll mediated maternal-fetal immune tolerance, which leads to influence on Th1/Th17 cell balance. We hope to revealve role of TRIM38 in maternal-fetal immune tolerance to provide new insight into treatment and diagnosis of infertility related disease.