英国剑桥大学Ashley Moffett等研究人员合作发现，人类子宫自然杀伤细胞调节妊娠早期滋养层外滋养细胞的分化。2024年1月17日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员利用滋养细胞器官组织和原始组织样本，来确定了子宫自然杀伤细胞（uNK）细胞如何影响胎盘。通过使用单细胞转录组学定位滋养层细胞和uNK细胞之间潜在的相互作用轴，并在体外模拟有机体中的这些相互作用，研究人员确定了一种uNK细胞衍生的细胞因子信号，它能在侵入途径的晚期促进滋养层细胞分化。

此外，它还会影响参与调节血流、营养、炎症和适应性免疫反应的转录程序，以及与先兆子痫等妊娠疾病相关的基因特征。这些研究结果表明了，uNK细胞与滋养层细胞之间的最佳免疫学相互作用机制如何提高生殖成功率。

据悉，在人类中，滋养层细胞均衡地侵入子宫粘膜（蜕膜）是成功怀孕的关键。有证据表明，这一过程受到uNK的调控，但它们如何影响生殖结果尚不清楚。

附：英文原文

Title: Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy

Author: Qian Li, Andrew Sharkey, Megan Sheridan, Elisa Magistrati, Anna Arutyunyan, Oisin Huhn, Carmen Sancho-Serra, Holly Anderson, Naomi McGovern, Laura Esposito, Ridma Fernando, Lucy Gardner, Roser Vento-Tormo, Margherita Yayoi Turco, Ashley Moffett

Issue&Volume: 2024-01-17

Abstract: In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success.

DOI: 10.1016/j.stem.2023.12.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00443-5