Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface
Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between P...
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/100002 |
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| author | Haiyi Fei Xiaowen Lu Zhan Shi Xiu Liu Cuiyu Yang Xiaohong Zhu Yuhan Lin Ziqun Jiang Jianmin Wang Dong Huang Liu Liu Songying Zhang Lingling Jiang |
| author_facet | Haiyi Fei Xiaowen Lu Zhan Shi Xiu Liu Cuiyu Yang Xiaohong Zhu Yuhan Lin Ziqun Jiang Jianmin Wang Dong Huang Liu Liu Songying Zhang Lingling Jiang |
| author_sort | Haiyi Fei |
| collection | DOAJ |
| description | Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE. |
| format | Article |
| id | doaj-art-a94e9cb1545544ffbe80771f879c8dcf |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-a94e9cb1545544ffbe80771f879c8dcf2025-08-20T02:48:42ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.100002Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interfaceHaiyi Fei0https://orcid.org/0009-0002-3344-070XXiaowen Lu1Zhan Shi2Xiu Liu3Cuiyu Yang4Xiaohong Zhu5Yuhan Lin6Ziqun Jiang7Jianmin Wang8Dong Huang9Liu Liu10Songying Zhang11https://orcid.org/0000-0001-8044-6237Lingling Jiang12https://orcid.org/0000-0002-3343-6279Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaDepartment of Obstetrics and Gynecology, Zhejiang Xiaoshan Hospital, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Reproductive Health and Disease, Hangzhou, China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, ChinaPreeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.https://elifesciences.org/articles/100002preeclampsiamaternal–fetal immunityCyTOFscRNA sequencingmacrophages |
| spellingShingle | Haiyi Fei Xiaowen Lu Zhan Shi Xiu Liu Cuiyu Yang Xiaohong Zhu Yuhan Lin Ziqun Jiang Jianmin Wang Dong Huang Liu Liu Songying Zhang Lingling Jiang Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface eLife preeclampsia maternal–fetal immunity CyTOF scRNA sequencing macrophages |
| title | Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface |
| title_full | Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface |
| title_fullStr | Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface |
| title_full_unstemmed | Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface |
| title_short | Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface |
| title_sort | deciphering the preeclampsia specific immune microenvironment and the role of pro inflammatory macrophages at the maternal fetal interface |
| topic | preeclampsia maternal–fetal immunity CyTOF scRNA sequencing macrophages |
| url | https://elifesciences.org/articles/100002 |
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