# T Cells and IL-9 Signaling at the Maternal-Fetal Interface in Preterm Labor and Birth

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $545,686

## Abstract

PROJECT SUMMARY
Approximately 70% of preterm births are preceded by preterm labor, which is primarily associated with non-
infectious etiologies. However, little is known about the non-acute-inflammatory causes of preterm birth. This
project builds on extensive published and preliminary data indicating that T cells and the cytokine IL-9 at the
maternal-fetal interface play an important role in preterm labor and birth. The overall goals of this project are to
define the mechanisms by which the cytokine IL-9 at the maternal-fetal interface promotes preterm birth and
negative consequences for offspring, to determine the mechanisms by which vitamin D can prevent these
outcomes, and to identify new T cell subtypes that contribute to preterm labor in humans. Aim 1 is to elucidate
the mechanisms by which IL-9 promotes preterm labor and birth. This aim tests the hypothesis that IL-9 targets
both hematopoietic and non-hematopoietic cells at the maternal-fetal interface in mice. Aim 1 will also explore
whether IL-9 signaling is required within the maternal or fetal tissues to promote preterm birth. Additionally, the
mechanisms whereby vitamin D prevents IL-9-induced preterm birth in mice will be determined. Aim 2 is to
define the impact on offspring of IL-9 at the maternal-fetal interface. This aim tests the hypothesis that maternal
IL-9 that enters the amniotic cavity causes adverse fetal and neonatal outcomes. Specifically, this aim will
examine the fetal lung, intestine, and placenta and neonatal airway and gut immunity. Additionally, the extent
to which prenatal vitamin D supplementation can mitigate the impact of in utero IL-9 exposure will be
investigated. A hypothesis-generating Aim 3 will identify T-cell subsets at the maternal-fetal interface in women
with preterm labor and birth. This project will make use of an advanced mouse model of IL-9-induced preterm
birth, imaging mass cytometry, spatial transcriptomics, single-cell RNA sequencing of human placenta samples
from term and preterm pregnancies, and functional testing on T cells isolated from patients with term or
preterm birth. The innovative fusion of immunology and omics approaches used here will unveil non-infectious
causes of preterm labor and birth and may lead to development of a treatment – such as vitamin D, which is
FDA-approved during pregnancy – to reduce the risk of preterm birth. Additionally, the new immune targets
identified could lead to development of novel strategies to reduce preterm birth and its sequelae. This project is
directly relevant to the call for research “exploring the contribution of immune dysregulation to gestational
disorders and adverse pregnancy outcomes” to improve reproductive health.

## Key facts

- **NIH application ID:** 10945667
- **Project number:** 1R01AI184481-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Nardhy Gomez-Lopez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $545,686
- **Award type:** 1
- **Project period:** 2024-08-17 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945667

## Citation

> US National Institutes of Health, RePORTER application 10945667, T Cells and IL-9 Signaling at the Maternal-Fetal Interface in Preterm Labor and Birth (1R01AI184481-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10945667. Licensed CC0.

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