In vivo generation of decidual natural killer cells from resident hematopoietic progenitors
In vivo generation of decidual natural killer cells from resident hematopoietic progenitors
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DOI：
10.3324/haematol.2013.091421
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发表时间：
2014-03-01
期刊：
影响因子：
10.1
通讯作者：
Mingari, Maria Cristina
中科院分区：
文献类型：
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作者：
Chiossone, Laura;Vacca, Paola;Mingari, Maria Cristina
蜕膜自然杀伤细胞积聚在胎母界面，在成功怀孕中起着关键作用。然而，它们的起源仍然未知。它们是来自蜕膜吸收的外周自然杀伤细胞，还是代表了一种来自原位的独特群体？在此，我们在妊娠小鼠蜕膜和子宫中发现了自然杀伤前体。早在妊娠第4.5天，蜕膜和子宫中就出现了大量增殖的未成熟自然杀伤细胞。在这里，我们通过EGFP（+）小鼠外周血成熟自然杀伤细胞或前体的转移实验来研究蜕膜和子宫自然杀伤细胞的起源。结果表明，成熟的自然杀伤细胞不会迁移到蜕膜和子宫，而前体在这些器官中被募集并向自然杀伤细胞分化。此外，蜕膜和子宫自然杀伤细胞表现出独特的表型和功能特征。尽管它们的表型不成熟，但它们表达了高水平的激活Ly49D受体。此外，蜕膜和子宫自然杀伤细胞的细胞溶解能力差，产生少量的ifn - γ，同时释放参与新血管生成和组织重塑的因子（GM-CSF， VEGF, IP-10）。我们的数据揭示了蜕膜自然杀伤细胞的原位生成，并提供了小鼠和人类蜕膜自然杀伤细胞之间的重要相关性，从而可以进一步研究它们在妊娠相关疾病中的作用。
Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP(+) mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN-gamma, while they released factors (GM-CSF, VEGF, IP-10) involved in neo-angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases.