# Innate Allorecognition at the Maternal-Fetal Interface

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $587,714

## Abstract

Pregnancy is a maternal balancing act. To guarantee optimal lifetime reproductive success, the
mother must partition her resources between current and future pregnancies. Too little investment
in the current pregnancy compromises fetal survival, while too much investment lowers lifetime
reproductive success by compromising future pregnancies. We hypothesize here that immune
system genes that encode activating and inhibitory allorecognition receptors on myeloid cells set
the optimum by balancing the maternal alloimmune response at the maternal-fetal interface.
Activating receptors limit trophoblast invasion and reduce maternal cost while inhibitory receptors
exert an opposite effect, resulting in an optimal balance. We also hypothesize that disrupting the
balance in either direction (in favor of the mother or in favor of the fetus) increases the risk of
gestational disorders such as preeclampsia. We will focus on allorecognition receptors expressed
on monocytes and macrophages that regulate the alloimmune response to transplanted organs
but have not been previously studied in gestation. In Aim 1, we will test the hypotheses in mice
by investigating the effect of deleting these receptors on the decidual immune landscape,
trophoblast invasion, placental function, and reproductive success, and assess if this results in
preeclampsia-like features. In Aim 2, we will test the hypotheses in humans by investigating the
association between preeclampsia and a maternal-fetal mismatch in the polymorphic gene
encoding one of these receptors that favors maternal myeloid cell activation. Particular attention
will be paid to the likely divergence of the immunopathogenesis of early and late preeclampsia,
which differ dramatically in placental pathology and effects on fetal growth. This grant proposal
brings together transplant immunologists, reproductive biologists, and preeclampsia experts to
execute the proposed aims.

## Key facts

- **NIH application ID:** 10947173
- **Project number:** 1R01AI184546-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fadi G. Lakkis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $587,714
- **Award type:** 1
- **Project period:** 2024-06-14 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947173

## Citation

> US National Institutes of Health, RePORTER application 10947173, Innate Allorecognition at the Maternal-Fetal Interface (1R01AI184546-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10947173. Licensed CC0.

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