母胎界面蜕膜NK细胞的表型和功能特征

项目名称： 母胎界面蜕膜NK细胞的表型和功能特征

项目编号： No.91442202

项目类型： 重大研究计划

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 魏海明

作者单位： 中国科学技术大学

项目金额： 300万元

中文摘要： 早孕蜕膜组织中免疫细胞占细胞总数的30-40%，其中NK细胞又占蜕膜免疫细胞总数的70%，如此大数量免疫细胞为何没有启动免疫应答，反而维持免疫耐受？回答该问题对认识正常妊娠的免疫耐受机制，以及免疫失常介导的妊娠相关疾病发病机理，会有重要指导意义。近十年来，我们对人蜕膜NK细胞已进行发育分化、功能极化研究并界定四种NK细胞亚群，本课题将进一步探讨以下问题：证明dNK细胞为CD56brightCD49a+ 特殊细胞群体，并受Lnc-56和Lnc-49的直接调控；聚焦1-2个dNK细胞关键负调分子，分析它们在维持母胎免疫耐受中的核心作用；探讨蜕膜dNK细胞如何接受HLA-I类分子的教育，形成对同种“异体”细胞的耐受，及其与正常妊娠/妊娠相关疾病的关联性。最终希望了解蜕膜微环境中免疫细胞尤其是NK细胞的动态特征，建立以dNK细胞为主体的母胎免疫界面细胞网络，促进对妊娠相关疾病发病机理的全面认识。

中文关键词： 母胎界面；自然杀伤细胞；功能；表型

英文摘要： In the process of embryonic development, special maternal-fetal interface is needed to protect the normal development of the fetus. Decidualization is the process of converting endometrial stromal cells into decidual cells and is the main characteristics of forming the maternal-fetal interface. In the deciduas of the first trimester, 30-40% of the total cells are immune cells, among which NK cells account for almost 70% of all the immune cells. Why such a large number of immune cells do not launch an immune response but maintain immune tolerance? Researches about this question will have great importance in our understanding in the immune tolerance mechanisms of the normal pregnancy and the pathogenesis of immune disorders mediated by pregnancy-related disease. In the recent ten years, we have researches on the differentiation and functional polarization of human decidual NK cells, and further identified four novel NK subsets. In this project, we will further discuss the following important issues: verify that decidual NK cells are special NK population with CD56brightCD49a+ phenotype and directly regulated by Lnc-56 and Lnc-49; focus on one or two key negative regulatory molecules on decidual NK cells and analyze their core role in maintaining maternal-fetal immune tolerance; explore how the decidual CD56brightCD49a+ NK cells accept educations of maternal or paternal HLA class I molecules and form tolerance for the allogenic cells; analysis of the binding sites and binding abilities between KIRs on NK cells and HLA-C from different individuals, and its correlation with normal pregnancy/pregnancy related diseases. Through these researches, we hope to eventually understand the dynamic characteristics of immune cells in decidual microenvironment, especially the main mechanism of the development, differentiation, mature, migration, education, activation and function of NK cells. These studies will hopefully establish the decidual NK cells dominated, novel immune cells network in maternal-fetal interface, which will further promote the comprehensive understanding of pregnancy-related disease pathogenesis.

英文关键词： the maternal-fetal interface; NK cells ;functional characterization ;Phenotypic characterization