Macrophages are crucial for a successful pregnancy, and malfunctions of decidual macrophages correlate with adverse pregnancyoutcomes, such as spontaneous abortion and preeclampsia. Previously, decidual macrophages we...Macrophages are crucial for a successful pregnancy, and malfunctions of decidual macrophages correlate with adverse pregnancyoutcomes, such as spontaneous abortion and preeclampsia. Previously, decidual macrophages were often thought to be a singlepopulation. In the present study, we identified three decidual macrophage subsets, CCR2−CD11cLO (CD11clow, ~80%), CCR2−CD11cHI (CD11chigh, ~5%), and CCR2+CD11cHI (CD11chigh, 10–15%), during the first trimester of human pregnancy by flowcytometry analysis. CCR2−CD11cLO macrophages are widely distributed in the decidua, while CCR2−CD11cHI and CCR2+CD11cHImacrophages are primarily detected close to extravillous trophoblast cells according to immunofluorescence staining. According toRNA sequencing bioinformatics analysis and in vitro functional studies, these three subsets of macrophages have differentphagocytic capacities. CCR2+CD11cHI macrophages have pro-inflammatory characteristics, while the CCR2−CD11cHI population issuggested to be anti-oxidative and anti-inflammatory due to its high expression of critical heme metabolism-related genes,suggesting that these two subsets of macrophages maintain an inflammatory balance at the leading edge of trophoblast invasionto facilitate the clearance of pathogen infection as well as maintain the homeostasis of the maternal-fetal interface. The presentstudy physiologically identifies three decidual macrophage subsets. Further clarification of the functions of these subsets willimprove our understanding of maternal-fetal crosstalk in the maintenance of a healthy pregnancy.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(81490741 and 81401224)the Ministry of Science and Technology of the People’s Republic of China(2016YFC1000208 and 2017YFC1001401).
文摘Macrophages are crucial for a successful pregnancy, and malfunctions of decidual macrophages correlate with adverse pregnancyoutcomes, such as spontaneous abortion and preeclampsia. Previously, decidual macrophages were often thought to be a singlepopulation. In the present study, we identified three decidual macrophage subsets, CCR2−CD11cLO (CD11clow, ~80%), CCR2−CD11cHI (CD11chigh, ~5%), and CCR2+CD11cHI (CD11chigh, 10–15%), during the first trimester of human pregnancy by flowcytometry analysis. CCR2−CD11cLO macrophages are widely distributed in the decidua, while CCR2−CD11cHI and CCR2+CD11cHImacrophages are primarily detected close to extravillous trophoblast cells according to immunofluorescence staining. According toRNA sequencing bioinformatics analysis and in vitro functional studies, these three subsets of macrophages have differentphagocytic capacities. CCR2+CD11cHI macrophages have pro-inflammatory characteristics, while the CCR2−CD11cHI population issuggested to be anti-oxidative and anti-inflammatory due to its high expression of critical heme metabolism-related genes,suggesting that these two subsets of macrophages maintain an inflammatory balance at the leading edge of trophoblast invasionto facilitate the clearance of pathogen infection as well as maintain the homeostasis of the maternal-fetal interface. The presentstudy physiologically identifies three decidual macrophage subsets. Further clarification of the functions of these subsets willimprove our understanding of maternal-fetal crosstalk in the maintenance of a healthy pregnancy.