Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss
Recurrent pregnancy loss (RPL) puzzles 1–3% of women of childbearing age worldwide. Immunological factors account for more than 60% of cases of unexplained RPL (URPL); however, the underlying mechanism remains unclear. Here, using single-cell sequencing data and functional experiments with clinical...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1045532/full |
| _version_ | 1798014211698196480 |
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| author | Yifei Sang Yifei Sang Yanhong Li Yanhong Li Ling Xu Ling Xu Jiajia Chen Jiajia Chen Dajin Li Dajin Li Meirong Du Meirong Du Meirong Du Meirong Du |
| author_facet | Yifei Sang Yifei Sang Yanhong Li Yanhong Li Ling Xu Ling Xu Jiajia Chen Jiajia Chen Dajin Li Dajin Li Meirong Du Meirong Du Meirong Du Meirong Du |
| author_sort | Yifei Sang |
| collection | DOAJ |
| description | Recurrent pregnancy loss (RPL) puzzles 1–3% of women of childbearing age worldwide. Immunological factors account for more than 60% of cases of unexplained RPL (URPL); however, the underlying mechanism remains unclear. Here, using single-cell sequencing data and functional experiments with clinical samples, we identified a distinct population of CCR1+ decidual macrophages (dMφ) that were preferentially enriched in the decidua from normal early pregnancies but were substantially decreased in patients with URPL. Specific gene signatures endowed CCR1+ dMφ with immunosuppressive and migration-regulatory properties, which were attenuated in URPL. Additionally, CCR1+ dMφ promoted epithelial-to-mesenchymal transition (EMT) to promote trophoblast migration and invasion by activating the ERK1/2 signaling pathway. Decidual stromal cell (DSC)-derived CCL8 was the key regulator of CCR1+ dMφ as CCL8 recruited peripheral CCR1+ monocytes, induced a CCR1+ dMφ-like phenotype, and reinforced the CCR1+ dMφ-exerted modulation of trophoblasts. In patients with URPL, CCL8 expression in DSCs was decreased and trophoblast EMT was defective. Our findings revealed that CCR1+ dMφ play an important role in immune tolerance and trophoblast functions at the maternal–fetal interface. Additionally, decreased quantity and dysregulated function of CCR1+ dMφ result in URPL. In conclusion, we provide insights into the crosstalk between CCR1+ dMφ, trophoblasts, and DSCs at the maternal–fetal interface and macrophage-targeted interventions of URPL. |
| first_indexed | 2024-04-11T15:14:57Z |
| format | Article |
| id | doaj.art-771fe11e4b31432cbe5243348e4cae18 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T15:14:57Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-771fe11e4b31432cbe5243348e4cae182022-12-22T04:16:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10455321045532Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy lossYifei Sang0Yifei Sang1Yanhong Li2Yanhong Li3Ling Xu4Ling Xu5Jiajia Chen6Jiajia Chen7Dajin Li8Dajin Li9Meirong Du10Meirong Du11Meirong Du12Meirong Du13National Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaNational Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaNational Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaNational Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaNational Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaNational Health Council (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, Macau SAR, ChinaRecurrent pregnancy loss (RPL) puzzles 1–3% of women of childbearing age worldwide. Immunological factors account for more than 60% of cases of unexplained RPL (URPL); however, the underlying mechanism remains unclear. Here, using single-cell sequencing data and functional experiments with clinical samples, we identified a distinct population of CCR1+ decidual macrophages (dMφ) that were preferentially enriched in the decidua from normal early pregnancies but were substantially decreased in patients with URPL. Specific gene signatures endowed CCR1+ dMφ with immunosuppressive and migration-regulatory properties, which were attenuated in URPL. Additionally, CCR1+ dMφ promoted epithelial-to-mesenchymal transition (EMT) to promote trophoblast migration and invasion by activating the ERK1/2 signaling pathway. Decidual stromal cell (DSC)-derived CCL8 was the key regulator of CCR1+ dMφ as CCL8 recruited peripheral CCR1+ monocytes, induced a CCR1+ dMφ-like phenotype, and reinforced the CCR1+ dMφ-exerted modulation of trophoblasts. In patients with URPL, CCL8 expression in DSCs was decreased and trophoblast EMT was defective. Our findings revealed that CCR1+ dMφ play an important role in immune tolerance and trophoblast functions at the maternal–fetal interface. Additionally, decreased quantity and dysregulated function of CCR1+ dMφ result in URPL. In conclusion, we provide insights into the crosstalk between CCR1+ dMφ, trophoblasts, and DSCs at the maternal–fetal interface and macrophage-targeted interventions of URPL.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1045532/fulldecidual macrophagesCCR1CCL8trophoblastsepithelial-to-mesenchymal transitionunexplained recurrent pregnancy loss |
| spellingShingle | Yifei Sang Yifei Sang Yanhong Li Yanhong Li Ling Xu Ling Xu Jiajia Chen Jiajia Chen Dajin Li Dajin Li Meirong Du Meirong Du Meirong Du Meirong Du Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss Frontiers in Immunology decidual macrophages CCR1 CCL8 trophoblasts epithelial-to-mesenchymal transition unexplained recurrent pregnancy loss |
| title | Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| title_full | Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| title_fullStr | Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| title_full_unstemmed | Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| title_short | Dysfunction of CCR1+ decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| title_sort | dysfunction of ccr1 decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss |
| topic | decidual macrophages CCR1 CCL8 trophoblasts epithelial-to-mesenchymal transition unexplained recurrent pregnancy loss |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1045532/full |
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