Inhibition of NFAT after human uterus transplant promotes loss of tissue-resident NK cells and attendant pregnancy complications [scRNA-seq]

Although mouse models have demonstrated that uNK cell deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here, we compared tissue samples collected from a cohort of human recipients of uterus transplant (UTx) at high risk for pregnancy complications with healthy controls using flow cytometry, immunofluorescence microscopy, and single-cell RNA sequencing (scRNA-seq).

Subsets of tissue-resident uNK cells were reduced in endometrial and decidual samples from recipients of UTx compared with healthy control samples. Loss of tissue-resident uNK cells was associated with histopathologic evidence of maternal vascular malperfusion in placentas from recipients of UTx and related pregnancy complications including preeclampsia. scRNA-seq of UTx endometrial biopsies and deciduae further revealed that the NK cell reduction in recipients of UTx correlated with impaired transcriptional programming of NK tissue residency arising from the inhibition of signaling by nuclear factor of activated T cells (NFAT).