免疫学异常是导致母-胎免疫耐受失衡的重要原因。本课题组前期工作已证实Toll 样受体参与了母-胎免疫耐受失衡的发生，但对于该过程母-胎界面树突状细胞Toll 样受体如何调节的机制尚不明确。本课题组最新研究证实去泛素化酶USP25是调控Toll 样受体转录因子的重要蛋白。申请者拟采用染色质免疫共沉淀技术、凝胶电泳漂移、靶基因验证等技术，利用体内动物模型及体外模型，并以USP25/TRAF3为靶点，构建shRNA慢病毒载体，探讨从不同层面阻断及过表达USP25、TRAF3、USP25/TRAF3对调节母-胎界面树突状细胞Toll 样受体分化参与妊娠母-胎耐受的机制。揭示这些蛋白与母-胎免疫识别和耐受的关系，阐明USP25与TRAF3相互作用的模式，解析这些蛋白所参与的信息转导通路中上、下游关键基因的相互关系，丰富和发展母-胎免疫识别和免疫豁免理论，为提高妊娠相关疾病预防和诊治水平提供科学依据。

Immune abnormality is important reason in maternal-fetal immune imbalance. Our previous study proves that Toll receptor involves in development of maternal-fetal immune imbalance, but the role of toll like receptor is unclear. We recently proved that deubiquitinating enzyme USP25 is the key regulator protein of toll like receptor transcriptional factor. We want to reveale the inner mechanism by co-immunoprepitation, gel electrophoresis, target gene implication both in-vivo and in-vitro level targeted at USP25/TRAF3 by shRNA interruption. We hope to explore role of USP25,TRAF3 and USP25/TRAF3 in regulating regulating Toll mediated maternal-fetal immune tolerance. Hoping we can enrich and develop maternal-fetal recognition theory and provide new insight into treatment and diagnosis of pregnancy related disease.