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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

TitleHuman CD56<sup>+</sup>CD39<sup>+</sup> dNK cells support fetal survival through controlling trophoblastic cell fate: Immune mechanisms of recurrent early pregnancy loss
Authors
Keywordsadoptive transfer
CD56 CD39 dNK subset + +
M-CSF
NOG mice
placental trophoblast cell fate
recurrent pregnancy loss
Issue Date2024
Citation
National Science Review, 2024, v. 11, n. 6, article no. nwae142 How to Cite?
AbstractDecidual 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 Identifierhttp://hdl.handle.net/10722/355333
ISSN
2023 Impact Factor: 16.3
2023 SCImago Journal Rankings: 2.934

 

DC FieldValueLanguage
dc.contributor.authorJia, Wentong-
dc.contributor.authorMa, Liyang-
dc.contributor.authorYu, Xin-
dc.contributor.authorWang, Feiyang-
dc.contributor.authorYang, Qian-
dc.contributor.authorWang, Xiaoye-
dc.contributor.authorFan, Mengjie-
dc.contributor.authorGu, Yan-
dc.contributor.authorMeng, Ran-
dc.contributor.authorWang, Jian-
dc.contributor.authorLi, Yuxia-
dc.contributor.authorLi, Rong-
dc.contributor.authorShao, Xuan-
dc.contributor.authorWang, Yan Ling-
dc.date.accessioned2025-04-03T02:00:06Z-
dc.date.available2025-04-03T02:00:06Z-
dc.date.issued2024-
dc.identifier.citationNational Science Review, 2024, v. 11, n. 6, article no. nwae142-
dc.identifier.issn2095-5138-
dc.identifier.urihttp://hdl.handle.net/10722/355333-
dc.description.abstractDecidual 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.languageeng-
dc.relation.ispartofNational Science Review-
dc.subjectadoptive transfer-
dc.subjectCD56 CD39 dNK subset + +-
dc.subjectM-CSF-
dc.subjectNOG mice-
dc.subjectplacental trophoblast cell fate-
dc.subjectrecurrent pregnancy loss-
dc.titleHuman CD56<sup>+</sup>CD39<sup>+</sup> dNK cells support fetal survival through controlling trophoblastic cell fate: Immune mechanisms of recurrent early pregnancy loss-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/nsr/nwae142-
dc.identifier.scopuseid_2-s2.0-85198015415-
dc.identifier.volume11-
dc.identifier.issue6-
dc.identifier.spagearticle no. nwae142-
dc.identifier.epagearticle no. nwae142-
dc.identifier.eissn2053-714X-

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