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Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.
- Source :
- National Science Review; Jun2024, Vol. 11 Issue 6, p1-17, 17p
- Publication Year :
- 2024
-
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-2Rγ<superscript>null</superscript>) 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<superscript>+</superscript>CD39<superscript>+</superscript> dNK cells. Mechanistic studies revealed that CD56<superscript>+</superscript>CD39<superscript>+</superscript> 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<superscript>+</superscript>CD39<superscript>+</superscript> dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20955138
- Volume :
- 11
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- National Science Review
- Publication Type :
- Academic Journal
- Accession number :
- 178321300
- Full Text :
- https://doi.org/10.1093/nsr/nwae142