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Three macrophage subsets are identified in the uterus during early human pregnancy

Cellular & Molecular Immunology 2018年第12期15卷 1027-1037页

作者： Xiangxiang Jiang Mei-Rong Du Min Li Hongmei Wang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Laboratory for Reproductive Immunology Hospital of Obstetrics and GynecologyFudan University Shanghai Medical CollegeShanghai 200011China Department of Obstetrics and Gynecology Navy General Hospital of the Chinese PLABeijing 100048China

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.

关键词： CCR2 CD11c decidual macrophage subsets extravillous trophoblast cells inflammatory balance

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