Abundant decidual natural killer (dNK) cells at the maternal-fetal interface are important during early pregnancy. However, functional subsets of dNK cells remain poorly understood. We describe a CD49a⁺PBX homeobox 1 (PBX1)⁺ dNK cell subset that promotes fetal development in humans and mice. The expression of PBX1 in dNK cells is up-regulated via the activated AKT1 pathway through the interaction of major histocompatibility complex G with the immunoglobulin-like transcript 2 receptor. PBX1 drives pleiotrophin and osteoglycin transcription in dNK cells, further promoting fetal development. Decreased PBX1 expression or the PBX1^G21S mutant correlated with fetal growth restriction and pregnancy failure in patients with unexplained recurrent spontaneous abortion (URSA). Inactivation of Pbx1 in mouse dNK cells impairs fetal development by decreasing growth-promoting factors from CD49a⁺PBX1⁺ dNK cells. Impairment of PBX1 in dNK cells has positive correlation with URSA pathogenesis and may provide a potential marker for this condition.

在孕早期，母婴界面的蜕膜自然杀伤细胞（dNK）丰富，这一点很重要。但是，dNK细胞的功能子集仍然知之甚少。我们描述了CD49a ⁺ PBX同源盒1（PBX1）⁺ dNK细胞亚群，可促进人类和小鼠的胎儿发育。dNK细胞中PBX1的表达通过主要的组织相容性复合物G与免疫球蛋白样转录物2受体的相互作用，通过激活的AKT1途径上调。PBX1在dNK细胞中驱动多效性蛋白和骨糖蛋白转录，从而进一步促进胎儿发育。PBX1表达降低或PBX1 ^G21S该突变与原因不明的反复自然流产（URSA）患者的胎儿生长受限和妊娠失败有关。小鼠dNK细胞中Pbx1的失活通过降低CD49a ⁺ PBX1 ⁺ dNK细胞的生长促进因子而损害胎儿发育。dNK细胞中PBX1的损伤与URSA发病机理呈正相关，可能为这种情况提供潜在的标志物。