Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome
| Title: | Targeting CD301+ macrophages inhibits endometrial fibrosis and improves pregnancy outcome |
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| Authors: | Haining Lv, Haixiang Sun, Limin Wang, Simin Yao, Dan Liu, Xiwen Zhang, Zhongrui Pei, Jianjun Zhou, Huiyan Wang, Jianwu Dai, Guijun Yan, Lijun Ding, Zhiyin Wang, Chenrui Cao, Guangfeng Zhao, Yali Hu |
| Source: | EMBO Molecular Medicine, Vol 15, Iss 9, Pp 1-19 (2023) |
| Publisher Information: | Springer Nature, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine (General) LCC:Genetics |
| Subject Terms: | CD301+ macrophages, endometrial fibrosis, intrauterine adhesion, pregnancy outcome, Medicine (General), R5-920, Genetics, QH426-470 |
| More Details: | Abstract Macrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single‐cell RNA sequencing, bulk RNA sequencing, and experimental verification. Increasing CD301+ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis, and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301+ macrophages secreted GAS6 to activate the AXL/NF‐κB pathway, upregulating the profibrotic protein synthesis. Targeted deletion of CD301+ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301+ macrophages for treating endometrial fibrosis. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1757-4676 1757-4684 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202317601 |
| Access URL: | https://doaj.org/article/140882d6042c44ef84d10e0a062db737 |
| Accession Number: | edsdoj.140882d6042c44ef84d10e0a062db737 |
| Database: | Directory of Open Access Journals |
| ISSN: | 17574676 17574684 |
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| DOI: | 10.15252/emmm.202317601 |
| Published in: | EMBO Molecular Medicine |
| Language: | English |