Biology subjects

Richter, H. E.

Publications and source records attributed to Richter, H. E..

2 recordsLinked to original sources

bioRxiv2025

A developmental program of early residency promotes the differentiation of divergent uterine NK cell subsets in humans

Human uterine natural killer cells (uNKs) are a tissue-resident, innate lymphocyte population that have critical roles in supporting pregnancy health. uNKs derive from circulatory cells in the peripheral blood which immigrate into the endometrium and become resident as they reconstitute the uterine lining after menses. How tissue-resident uterine NK cells arise from blood-based precursor cells is unknown. Here, we identify early tissue immigrants, developmental intermediates, and mature effector states in human endometrium. We also uncover a transcriptional program of TGF-{beta} responsive genes that is upregulated in recent tissue immigrants prior to expression of effector molecules. Differences in TGF-{beta} responsiveness of uNK precursors promote differential expression of divergent effector uNK subsets, resulting in either repression or preservation of cytotoxic effector potential. Collectively, these data suggest a molecular mechanism of tissue-resident uNK maturation that links tissue residency with the acquisition of divergent effector functions in human endometrium.

immunology↗

bioRxiv2024

Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced uNK cells and altered pregnancy phenotypes. We show that the NK reduction in UTx correlates with impaired transcriptional programming of NK tissue residency arising from the inhibition of NFAT-mediated signaling. Our observations suggest that NFAT-dependent genes modulate multiple molecular tissue residency programs in uNKs. These include early residency programs involving AP-1-family transcription factors and TGF-{beta}-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence SummaryRole of NFAT in uterine NK cell tissue residency

immunology↗