蜕膜CXCR4+与CXCR4-NK细胞在CD4+T细胞亚群平衡与母-胎免疫耐受中的调节作用

蜕膜NK细胞与CD4+T细胞亚群平衡在母-胎免疫耐受与正常妊娠维持中至关重要。我们前期发现蜕膜局部存在CXCR4+与CXCR4-具有不同表型的CD56brightNK细胞亚群，分别是IL-4与IFN-γ的主要来源，有趣的是自然流产蜕膜CXCR4+CD56brightNK细胞数量及其IL-4产生下降，伴随母-胎界面CD4+T细胞亚群失衡，提示蜕膜CXCR4+与CXCR4- NK细胞在局部CD4+T细胞亚群平衡与正常妊娠维持中至关重要。本课题以绒毛外滋养细胞募集的外周血CXCR4+NK为研究对象，通过细胞共培养、组学筛选与信息学分析、不同荧光标记与过继转输等策略并应用正常妊娠与自然流产标本与动物模型以及NK缺陷小鼠解析蜕膜CXCR4+与CXCR4-NK细胞亚群在局部富集、分化及其对CD4+T细胞分化的调节机制，阐明母-胎免疫耐受机制，为反复自然流产防治及寻求更有效的移植免疫策略提供理论依据。

Decidual NK cells and CD4+T cell subsets play important roles in maternal-fetal tolerance and normal pregnancy. We previously have demonstrated that there are two subsets of NK cells, which are CXCR4+ and CXCR4- CD56bright NK cells at the maternal-fetal interface. CXCR4-expressing CD56bright NK cells produce IL-4 and are the main source of IL-4 at the maternal-fetal interface. In contrast, CXCR4-CD56bright dNK produce more IFN-γ than CXCR4+CD56bright NK cells. Interestingly, the number of CXCR4+CD56bright dNK cell is less and its capacity of IL-4-producing is much lower in miscarriage, which is accompanied by disturbed CD4+T subset balance in the decidua. Therefore, we speculate that the CXCR4+CD56bright NK and CXCR4-CD56bright NK subsets are critical in the CD4+T cell subset balance and the maintenance of normal pregnancy. In the present study, we will study dNK cell enrichment and differentiation, and functional regulation of decidual NK cells on CD4+naive T cells by establishing cell-coculture system, proteomic screening, fluorescence labeling, adoptive transferring and different animal models. Our study will clarify the maternal-fetal immune regulation mechanism, supply important scientific basis for the therapy of human recurrent spontaneous abortion and look for more reasonable and efficient strategies of transplantation immunity.