PBX1 expression in uterine natural killer cells drives fetal growth.

Zhou, Yonggang; Fu, Binqing; Xu, Xiuxiu; Zhang, Jinghe; Tong, Xianhong; Wang, Yanshi; Dong, Zhongjun; Zhang, Xiaoren et al. · Sci Transl Med · 2020

basic_science · Level V

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Abstract

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<sup>+</sup>PBX homeobox 1 (PBX1)<sup>+</sup> 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<sup>G21S</sup> mutant correlated with fetal growth restriction and pregnancy failure in patients with unexplained recurrent spontaneous abortion (URSA). Inactivation of <i>Pbx1</i> in mouse dNK cells impairs fetal development by decreasing growth-promoting factors from CD49a<sup>+</sup>PBX1<sup>+</sup> 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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