Placental macrophages: Their development and role in the placenta

胎盘是胎儿制造的第一个器官，是母亲和婴儿之间的界面。正常功能的胎盘对成功怀孕至关重要。巨噬细胞是所有器官健康功能的关键，它们采用特定的特性来满足它们所在组织的需要。霍夫鲍尔细胞（HBC）是胎盘绒毛树中发现的来自胎儿的巨噬细胞。然而，尽管它们是胎盘中唯一的免疫细胞，但它们的确切特征和功能尚不清楚。这些细胞早在受孕后18天就出现了，它们的高丰度表明它们在胎盘发育和功能中起着重要作用。由于它们位于这个重要的屏障部位，我们认为HBC也可以保护胎盘和胎儿免受感染。我最近发表的作品描述了HBC及其前体。我们还定义了胎盘相关的母体巨噬细胞（PAMM）群体，它们来自于绒毛间隙的母体单核细胞。PAMM被发现粘附在合胞体的损伤部位，滋养层的外层。我的工作为人类胎盘巨噬细胞群体的研究提供了一个重要的框架。本研究计划将确立人类胎盘作为一个独特的血液学生态位（目的1），并将确定乙肝病毒在妊娠早期和晚期如何调节滋养细胞生物学（目的2）。最后，我们将确定胎盘巨噬细胞在两个重要的全球性问题中的作用，即产妇肥胖（目的2）和经胎盘感染，重点关注主要的垂直传播病原体，人类巨细胞病毒（目的3）。这些研究目标将通过我的实验室开发的测序技术和体外测定来实现。通过增加我们对HBC的了解，将会出现关于人类胎盘发育及其如何支持妊娠障碍的新见解。

The placenta, the first organ the fetus makes, is the interface between the mother and baby. A normally functioning placenta is crucialfor successful pregnancy. Macrophages are key to the healthy function of all organs, adopting specific properties to meet the needs ofthe tissue where they reside. Hofbauer cells (HBC) are fetal-derived macrophages found within the placental villous tree. However,their exact characteristics and functions are quite obscure despite being the only placental immune cell. The early appearance ofthese cells at 18 days post conception and their high abundance indicates that they play an important role in placental developmentand function. As they are located at this important barrier site, we propose that HBC also protect the placenta and fetus frominfection.My recent published work has characterised HBC and their precursors. We also defined a population of placental associated maternalmacrophages (PAMM), that are derived from maternal monocytes in the intervillous space. PAMM are found adhered to sites ofdamage on the syncytium, the outer trophoblast layer. My work has provided an important framework for the study of humanplacental macrophage populations.This research proposal will establish the human placenta as a unique haematological niche (Aim 1) and will determine how HBCregulate trophoblast biology in both early and late pregnancy (Aim 2). Finally, we will establish the roles of placental macrophages intwo important global problems, maternal obesity (Aim 2) and transplacental infection, focusing on the major vertically transmittedpathogen, human cytomegalovirus (Aim 3). These research objectives will be achieved through sequencing techniques and in vitroassays developed in my lab.By increasing our understanding of HBC new insights will emerge about human placental development and how this underpinspregnancy disorders.