# Tissue-resident NK cell development and function in pregnancy and transplantation: lessons learned from human uterus transplant recipients

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $678,289

## Abstract

The overarching goal of this project is to improve our mechanistic understanding of
pregnancy complications in organ transplant recipients. By studying a patient population
with increased risks of pre-eclampsia and fetal growth restriction, this project fills critical
knowledge gaps in reproductive immunology and improves the health of all women.
Pregnancy in organ transplant recipients has historically been difficult to study because
reproductive age females represent a minority of transplant recipients and pregnancy has
been discouraged given concerns around maternal and fetal health. We overcome these
prior limitations by leveraging our access to a unique cohort of transplant recipients who
receive a uterus transplant for the express purpose of gestation and delivery. Notably,
uterus transplant recipients have high rates of pre-eclampsia and other disorders of
placentation, which may be due to perturbations in natural killer cell biology as these cells
play critical roles in spiral artery remodeling and placentation. Hence, defects in uNK
development, homeostasis, and function likely contribute to the pathogenesis of
pregnancy complications. Importantly, our prior studies suggest that immunosuppression
medications that transplant recipients receive may impact the survival, localization, and
function of uterine natural killer cells, thereby providing mechanistic insights into why
pregnancy complications in organ transplant recipients are frequent. Notably, the
alterations we have observed in uterine NK cells in uterus transplant recipients associate
with abnormal placental histology and have had clinical consequences. In this proposal,
we thus build upon these findings to better understand the molecular mechanisms
underpinning defects in uNK development, homeostasis and function using uterus
transplantation as a model system. We accomplish these goals by analyzing endometrial
biopsies from uterus transplant recipients as well as healthy controls using state-of-the-
art single-cell technologies (i.e., single cell RNA-sequencing, single-nuclear RNA-seq;
CITE-seq) alongside high dimensional, multi-parameter flow cytometry and imaging
studies (i.e., immunofluorescence microscopy and spatial transcriptomics). These
experiments using human samples are complemented by in vivo mouse studies where
placentation in the setting of immunosuppression can be better studied across all phases
of pregnancy.

## Key facts

- **NIH application ID:** 10979790
- **Project number:** 1R01AI177369-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** PAIGE M PORRETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $678,289
- **Award type:** 1
- **Project period:** 2024-06-06 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979790

## Citation

> US National Institutes of Health, RePORTER application 10979790, Tissue-resident NK cell development and function in pregnancy and transplantation: lessons learned from human uterus transplant recipients (1R01AI177369-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10979790. Licensed CC0.

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