Beyond Maternal Tolerance: Education of Uterine Natural Killer Cells by Maternal MHC Drives Fetal Growth.
Beyond Maternal Tolerance: Education of Uterine Natural Killer Cells by Maternal MHC Drives Fetal Growth.
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DOI：
10.3389/fimmu.2022.808227
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
生殖免疫学已经从 60 年前梅达沃的经典问题“母亲为什么不排斥胎儿？”继续发展。除了胎儿-母体耐受性之外，现代生殖免疫学还关注母体免疫系统如何支持胎儿生长。母体子宫自然杀伤（uNK）细胞与胎儿滋养层细胞合作，调节孕妇和小鼠子宫的生理血管变化。这些血管变化对于构建胎盘和维持胎儿生长是必要的。子宫和其他地方的 NK 细胞功能，包括主要由血液 NK 细胞介导的抗病毒和抗肿瘤免疫，受到 NK 细胞教育的调节，这是一个确定细胞激活阈值的可量化过程。这个过程很大程度上依赖于自身 MHC I 类分子和抑制性 NK 细胞受体之间的相互作用。通过了解自我，母体免疫系统会设置 uNK 细胞参与子宫内的组织稳态。胎盘植入可以被视为脊椎动物中独特的自然移植形式，这提出了一个问题：uNK 细胞教育或缺失自我识别如何影响其功能并最终影响胎儿生长。在这里，通过使用 MHC 充足和缺乏的小鼠的组合，我们表明 uNK 细胞教育与母体而不是胎儿 MHC 有关，因此 MHC 缺陷的母鼠会产生更多生长受限的胎儿，即使胎儿本身表达自身 MHC。我们还表明，虽然外周 NK 细胞根据缺失自我识别的既定规则排斥骨髓细胞，但受母体 MHC 教育的 uNK 细胞不会排斥缺失自我 MHC 的胎儿，并且这些胎儿充分发挥潜力。虽然这些结果并不直接适用于临床研究，但它们表明母体 MHC-I 进行 NK 教育是胎儿最佳生长所必需的。
Reproductive immunology has moved on from the classical Medawar question of 60 years ago “why doesn’t the mother reject the fetus?”. Looking beyond fetal-maternal tolerance, modern reproductive immunology focuses on how the maternal immune system supports fetal growth. 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, including anti-viral and anti-tumour immunity mediated mostly by blood NK cells, 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. By getting to know self, the maternal immune system sets up uNK cells to participate to tissue homeostasis in the womb. Placentation can be viewed as a form of natural transplantation unique in vertebrates and this raises the question of how uNK cell education or missing-self recognition affect their function and, ultimately fetal growth. Here, using combinations of MHC-sufficient and -deficient mice, we show that uNK cell education is linked to maternal and not fetal MHC, so that 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. While these results are not directly applicable to clinical research, they show that NK education by maternal MHC-I is required for optimal fetal growth.
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影响因子：
15.3
作者：
Ashkar, A A;Di Santo, J P;Croy, B A
通讯作者：
Croy, B A
影响因子：
4
作者：
Goldman-Wohl, DS;Ariel, I;Yagel, S
通讯作者：
Yagel, S
影响因子：
6.1
作者：
Hiby, S. E.;Regan, L.;Moffett, A.
通讯作者：
Moffett, A.
影响因子：
7.3
作者：
Boulenouar S;Doisne JM;Sferruzzi-Perri A;Gaynor LM;Kieckbusch J;Balmas E;Yung HW;Javadzadeh S;Volmer L;Hawkes DA;Phillips K;Brady HJ;Fowden AL;Burton GJ;Moffett A;Colucci F
通讯作者：
Colucci F
影响因子：
5.4
作者：
Andersson, Katja E.;Williams, Geoffrey S.;Hoglund, Petter
通讯作者：
Hoglund, Petter