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- Publisher Website: 10.1093/nsr/nwae142
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Article: Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: Immune mechanisms of recurrent early pregnancy loss
Title | Human CD56<sup>+</sup>CD39<sup>+</sup> dNK cells support fetal survival through controlling trophoblastic cell fate: Immune mechanisms of recurrent early pregnancy loss |
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Authors | |
Keywords | adoptive transfer CD56 CD39 dNK subset + + M-CSF NOG mice placental trophoblast cell fate recurrent pregnancy loss |
Issue Date | 2024 |
Citation | National Science Review, 2024, v. 11, n. 6, article no. nwae142 How to Cite? |
Abstract | Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL. |
Persistent Identifier | http://hdl.handle.net/10722/355333 |
ISSN | 2023 Impact Factor: 16.3 2023 SCImago Journal Rankings: 2.934 |
DC Field | Value | Language |
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dc.contributor.author | Jia, Wentong | - |
dc.contributor.author | Ma, Liyang | - |
dc.contributor.author | Yu, Xin | - |
dc.contributor.author | Wang, Feiyang | - |
dc.contributor.author | Yang, Qian | - |
dc.contributor.author | Wang, Xiaoye | - |
dc.contributor.author | Fan, Mengjie | - |
dc.contributor.author | Gu, Yan | - |
dc.contributor.author | Meng, Ran | - |
dc.contributor.author | Wang, Jian | - |
dc.contributor.author | Li, Yuxia | - |
dc.contributor.author | Li, Rong | - |
dc.contributor.author | Shao, Xuan | - |
dc.contributor.author | Wang, Yan Ling | - |
dc.date.accessioned | 2025-04-03T02:00:06Z | - |
dc.date.available | 2025-04-03T02:00:06Z | - |
dc.date.issued | 2024 | - |
dc.identifier.citation | National Science Review, 2024, v. 11, n. 6, article no. nwae142 | - |
dc.identifier.issn | 2095-5138 | - |
dc.identifier.uri | http://hdl.handle.net/10722/355333 | - |
dc.description.abstract | Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL. | - |
dc.language | eng | - |
dc.relation.ispartof | National Science Review | - |
dc.subject | adoptive transfer | - |
dc.subject | CD56 CD39 dNK subset + + | - |
dc.subject | M-CSF | - |
dc.subject | NOG mice | - |
dc.subject | placental trophoblast cell fate | - |
dc.subject | recurrent pregnancy loss | - |
dc.title | Human CD56<sup>+</sup>CD39<sup>+</sup> dNK cells support fetal survival through controlling trophoblastic cell fate: Immune mechanisms of recurrent early pregnancy loss | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1093/nsr/nwae142 | - |
dc.identifier.scopus | eid_2-s2.0-85198015415 | - |
dc.identifier.volume | 11 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | article no. nwae142 | - |
dc.identifier.epage | article no. nwae142 | - |
dc.identifier.eissn | 2053-714X | - |