# ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $562,431

## Abstract

Epidemiological studies have associated preeclampsia outcomes with genotypes of receptors on maternal
natural killer (NK) cells, and genotypes of their cognate HLA class I (HLA-I) ligands in fetuses. These clinical
findings have been replicated and strongly suggest that uterine NK (uNK) cells, the most abundant leukocytes
at the maternal-fetal interface, specifically use their receptors to recognize HLA-I on fetal tissues, thereby
playing vital roles in normal placentation, probably by affecting the vasculature which is abnormal in
preeclampsia. Although it is challenging to study these possibilities in human reproduction, and we
acknowledge that there are species-specific differences between human and mouse pregnancy, studies of
mouse NK cells can yield important conceptual insight, as demonstrated numerous times previously in NK
cell biology. Recent studies from the applicant's laboratory indicate that mouse organs, including the virgin
uterus, contain both circulating “conventional” NK (cNK) cells and tissue-resident NK (trNK) cells that reside
in the organ and do not recirculate. cNK and trNK cells from different organs represent distinct lineages of NK
cells because they have differences in transcription factor dependencies. Moreover, cNK and trNK cells have
different functional capacities. Finally, the Ly49 family of receptors are the functional equivalents to the human
NK cell receptors implicated in preeclampsia. These considerations lead to the following proposed Specific
Aims: 1) Determine contributions of cNK and trNK cells to uNK cells in pregnancy and decidualization; 2)
Examine transcription factor dependence of uNK cells; and 3) Determine role of Ly49 receptors in pregnancy.
Thus, these studies will provide major insight into the role of uNK cells in pregnancy, the major long-term
objective of this proposal.

## Key facts

- **NIH application ID:** 10451584
- **Project number:** 5R01AI140397-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Wayne M. Yokoyama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $562,431
- **Award type:** 5
- **Project period:** 2018-08-13 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451584

## Citation

> US National Institutes of Health, RePORTER application 10451584, ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY (5R01AI140397-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10451584. Licensed CC0.

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