Education of uterine natural killer cells by maternal MHC drives fetal growth
| العنوان: | Education of uterine natural killer cells by maternal MHC drives fetal growth |
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| المؤلفون: | Delphine M Depierreux, Jens Kiekbush, Norman Shreeve, Andrew Sharkey, Delia Hawkes, Francesco Colucci |
| المصدر: | The Journal of Immunology. 208:59.13-59.13 |
| بيانات النشر: | The American Association of Immunologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Maternal uterine natural killer (uNK) cells, in partnership with fetal trophoblast cells, regulate physiological vascular changes in the uterus of pregnant women and mice. These vascular changes are necessary to build the placenta and sustain fetal growth. NK cell functions, in the uterus and elsewhere, are modulated by NK cell education, a quantifiable process that determines cellular activation thresholds. This process relies largely on interactions between self-MHC class I molecules and inhibitory NK cell receptors but its physiological importance has remained largely elusive. NK cell education during pregnancy is unique because uNK cells are exposed to both maternal and fetal MHC-I molecules. Here, we set out to answer the question of how uNK cell education or missing-self recognition affect their function and, ultimately, fetal growth. Using combinations of MHC-sufficient and -deficient mice, we show that maternal and not fetal MHC regulates uterine NK cell education in mice. MHC-deficient dams produce more growth-restricted fetuses, even when the fetuses themselves express self-MHC. We also show that, while peripheral NK cells reject bone marrow cells according to the established rules of missing-self recognition, uNK cells educated by maternal MHC do not reject fetuses that miss self-MHC and these fetuses grow to their full potential. Our data shed light on the physiological importance of uNK cell education: by getting to know self, the maternal immune system sets up uNK cells to participate to the womb tissue homeostasis and to contribute to reproductive success. This work was supported by the Cambridge NIHR BRC Cell Phenotyping Hub and by grants from the Wellcome Trust (094073/Z /10/Z), the MRC (MR/P001092/1) and the Centre for Trophoblast Research. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::9e181155748b7623864e46fb21d27b94 https://doi.org/10.4049/jimmunol.208.supp.59.13 |
| رقم الأكسشن: | edsair.doi...........9e181155748b7623864e46fb21d27b94 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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