小于胎龄儿（SGA）母胎界面免疫微环境的变化及其调节机制研究

The small for gestational age (SGA) have attracted much more attention of pediatrics and perinatology because of the rising incidence of a disease and poor long-term outcome. The etiology of SGA has not yet fully understood, which lacking effective treatment as well. The immune microenvironment of maternal-fetal interface is an important factor that maintaining normal pregnancy, and anomalous change of immune microenvironment may lead to many diseases associated with pregnancy including fetal growth restriction (FGR) and SGA. On the basis of our previous work, we will first focus on the quantity, phenotype, cytokine secretion and cytotoxicity of NK and γδ T cells, the main population of immune cells on maternal-fetal interface of SGA by immunohistochemistry and flow cytometry; Further, the effect of function of Sertoli cell by NK and γδ T cells and mutual adjustment mechanism will be studied by direct and indirect culture system in vitro, which confirming the importance of immune microenvironment changes on placenta and fetal growth and development. Our research achievements will help us obtaining more comprehensive understanding of immune microenvironment of SGA maternal-fetal interface, and also suggesting a new strategy to explore more effective prevention and correction of SGA.

小于胎龄儿（SGA）因其发病率的上升及远期结局差，已成为儿科学及围生医学不容忽视又迫切需要解决的问题。小于胎龄儿的发病原因至今未明，亦缺乏有效的救治措施。母-胎界面的免疫微环境是维持正常妊娠的重要因素，免疫微环境的异常变化可导致妊娠相关的多种疾病包括胎儿生长受限（FGR）及SGA的发生。本研究拟在课题组前期项目的工作基础上，首先通过免疫组化及流式细胞检测技术，对SGA母胎界面的主要免疫细胞群NK细胞及γδ T细胞的数量、分布、表型，以及它们的相关细胞因子分泌及细胞毒功能变化特征进行研究；再通过体外直接与间接的细胞共培养技术，进一步研究NK与γδ T细胞对滋养细胞功能的影响及相互调节的分子机制，从而证实免疫微环境变化对胎盘功能及胎儿生长发育的重要性。这些研究成果将有助于我们对SGA母胎界面的免疫微环境特征获得较全面的认识，也必将对临床探索更有效的预防和纠正SGA的诊治方法带来新的思路。

小于胎龄儿（small for gestational age,SGA）在生长发育诸多问题上有异于正常足月儿，其发病机制至今未明。母-胎界面的免疫微环境是维持正常妊娠的重要因素。本项目主要针对SGA这类特殊妊娠结局研究其蜕膜免疫细胞的变化特征，期望为临床更有效地预防和纠正SGA的发生发展提供新的切入点。研究结果显示，蜕膜NK细胞是蜕膜免疫细胞的优势细胞群，其表型以CD56brightCD16-细胞亚群为主，SGA蜕膜NK细胞的数量和比例、细胞因子分泌及细胞毒功能均较对照组发生明显改变；蜕膜γδT细胞以Vδ1亚型为主，但随着妊娠进展，Vδ1优势亚群比例下降，而Vδ2的比例上升，同时蜕膜γδT细胞明显高表达CD49a及CD69等组织驻留标志，显示出局部组织驻留特性；研究进一步通过体外共培养技术证实SGA母胎界面来源的蜕膜NK细胞对胎盘滋养细胞及血管内皮细胞的增殖、侵袭及成管功能的促进作用明显下降。这些结果高度提示母胎界面的免疫微环境因素参与了SGA的病理机制，尤其是蜕膜NK细胞不仅在数量上减少，更重要的是表现出多种生物学功能的明显不足，并通过对胎盘滋养细胞和血管内皮细胞的影响进一步影响胎儿生长发育。母胎界面免疫微环境的调控可能是有效预防与纠正小于胎龄儿的新策略。