Placental macrophages: Their development and role in the placenta

胎盘巨噬细胞：它们在胎盘中的发育和作用

• 批准号: EP/Y016262/1
• 负责人: Naomi McGovern
• 金额: $ 215.78万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY016262%2F1
• 关键词: Placental; macrophages; Their; development; role

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.

胎盘是胎儿制造的第一个器官，是母亲和婴儿之间的界面。一个功能正常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，采用特定的特性来满足它们所在组织的需求。Hofbauer细胞（HBC）是胎盘绒毛树中发现的胎儿来源的巨噬细胞。然而，尽管它们是唯一的胎盘免疫细胞，但它们的确切特性和功能相当模糊。这些细胞在受孕后18天早期出现，并且它们的高丰度表明它们在胎盘发育和功能中起重要作用。由于它们位于这个重要的屏障部位，我们认为HBC也保护胎盘和胎儿免受感染。我们还定义了一个胎盘相关的母体巨噬细胞（PAMM）群体，它们来源于绒毛间隙中的母体单核细胞。PAMM被发现粘附在合胞体（滋养层外层）的损伤部位。我的工作为人类胎盘巨噬细胞群的研究提供了一个重要的框架。这项研究计划将建立人类胎盘作为一个独特的血液生态位（目标1），并将确定HBC如何调节妊娠早期和晚期的滋养层生物学（目标2）。最后，我们将建立胎盘巨噬细胞在两个重要的全球性问题中的作用，母体肥胖（目标2）和经胎盘感染，重点是主要的垂直传播病原体，人巨细胞病毒（目标3）。这些研究目标将通过我实验室开发的测序技术和体外分析来实现。通过增加我们对HBC的理解，将出现关于人类胎盘发育及其如何支持妊娠障碍的新见解。