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Macrophage subsets at the maternal-fetal interface

Cellular & Molecular Immunology volume 17, pages 889–891 (2020)Cite this article

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Decidual macrophages account for 10–20% of decidual immune cells during early human pregnancy and have been reported to play roles in tissue remodeling, debris clearance, and parturition.1 Investigators consistently consider decidual macrophages a homogenous population in studies.2 By using CCR2 and CD11c, we divided decidual macrophages into three distinct subsets during early human pregnancy.3 CCR2-CD11cLO macrophages were the most abundant (~80%) macrophage subset and were evenly distributed in the decidua. CCR2 + CD11cHI macrophages (10–15%) were proinflammatory and mainly distributed proximal to extravillous trophoblast cells (EVTs). Remarkably, a novel decidual macrophage population, the heme oxygenase-1 positive (HMOX1+) macrophage subset (CCR2-CD11cHI), which was the lowest (~5%) of the three populations studied, was identified and found to be localized strictly proximal to EVTs. Here, we first report our experimental progress on decidual macrophage subsets and then discuss important studies related to the two CD11cHI macrophage subsets located proximal to EVTs.

The concepts of M1 and M2 macrophages have been well known in the field of macrophage research.1,6 Thus, we sought to elucidate the relationships between these three subsets of decidual macrophages and in vitro-induced M1 or M2 macrophages. M1 and M2 genes were defined based on highly expressed genes that showed at least a two-fold difference between M1 and M2 macrophages (Table S1) according to published RNA-Seq data (GSE36952).7 Based on the unsupervised clustering results, we found that CCR2 + CD11cHI macrophages expressed many more M1 macrophage genes and expressed these genes at higher levels than the other two decidual macrophage subsets (Fig. 1b). Furthermore, this CCR2+ macrophage subset clustered with M1 macrophages (Fig. 1c). Considering the proinflammatory properties of this subset, we suggest CCR2 + CD11cHI to be M1-like macrophages in vivo. The two CCR2− macrophage subsets always clustered together, regardless of whether M1 or M2 genes were used for evaluation (Fig. 1b–e), suggesting that the CCR2-CD11cLO and CCR2-CD11cHI macrophage subsets share more commonalities with each other than with the CCR2 + CD11cHI subset. Additionally, the expression levels and expression scale of M2 genes were much higher and much more extensive in these two CCR2- macrophage subsets than those of M1 genes (Fig. 1b, d). Therefore, we suggest that the CCR2-CD11cLO and CCR2-CD11cHI macrophage subsets are inclined to be anti-inflammatory M2-like macrophages; however, these two CCR2- subsets did not cluster with M2 macrophages. This might be explained by the discrepancy between the in vitro-induced macrophage type and the in vivo decidual macrophages, and it seemed unlikely that a particular in vivo macrophage population would be fully matched with the in vitro-induced M1 or M2 subtype.6 We suggest that because of the high percentage (>80%) of M2-like CCR2-CD11cLO macrophages at the maternal-fetal interface, decidual macrophages are usually considered the M2 type.8 Additionally, with the discovery of the three decidual macrophage subsets, investigators could easily detect the percentages of M1- and M2-like macrophages at the maternal-fetal interface, which may contribute to the investigation of gestational diseases that correlate with inflammatory factors.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (31900664 and 81671465) and the Ministry of Science and Technology of the People’s Republic of China (2018YFC1004101 and 2017YFC1001401).

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Authors and Affiliations

  1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China

    Xiangxiang Jiang & Hongmei Wang

  2. Innovation Academy for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China

    Xiangxiang Jiang & Hongmei Wang

  3. Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100049, China

    Hongmei Wang

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Correspondence to Xiangxiang Jiang or Hongmei Wang.

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Jiang, X., Wang, H. Macrophage subsets at the maternal-fetal interface. Cell Mol Immunol 17, 889–891 (2020). https://doi.org/10.1038/s41423-020-0435-6

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