Research ArticlePregnancy

PBX1 expression in uterine natural killer cells drives fetal growth

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Science Translational Medicine  01 Apr 2020:
Vol. 12, Issue 537, eaax1798
DOI: 10.1126/scitranslmed.aax1798

Natural killers’ gentler side

Numerous decidual natural killer cells are found at the maternal-fetal interface in the placenta during early pregnancy. Zhou et al. identified a transcription factor called PBX1, which is present in these natural killer cells and stimulates the production of growth-promoting factors, proteins needed for fetal growth and development. In pregnant mice, lack of functional PBX1 in decidual natural killer cells resulted in fetal growth restriction, which could be rescued by reintroducing wild-type PBX1. Human patients with a history of unexplained recurrent spontaneous abortion often had impaired activity of PBX1 in their decidual natural killer cells as well, offering a mechanistic explanation for their diagnosis.


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 PBX1G21S 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.

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