# IL17 mediates chorioamnionitis induced lung damage

> **NIH NIH K08** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $171,095

## Abstract

PROJECT SUMMARY
Chorioamnionitis (chorio) is the most common cause of preterm birth. Chorio increases the risk for fetal and
neonatal mortality and bronchopulmonary dysplasia (BPD). There are no effective therapies for preventing
preterm birth, chorio, or BPD. I have previously shown that preterm birth due to chorio is propagated by IL-1
receptor-associated kinase 1 (IRAK1). Preliminary data from my human and mouse transcriptome & cytokine
analysis demonstrate increased Th17 activation, and poor lung and cardiac function in mice exposed to chorio.
The central hypothesis is that chorio induces specific alterations of the fetal immune system via
stimulation of the IRAK1 pathway, resulting in lung parenchymal and vascular injury.
We will test the hypotheses with the following Specific Aims:
Specific Aim 1: To test the hypothesis that human infants exposed to chorio have increased Th17 cell
activation and subsequent pro-inflammatory cytokine generation leading to long-term adverse lung
function & pulmonary hypertension. I will conduct a prospective cohort study on 152 preterm infants (<32
weeks GA) (exposed and non-exposed to chorio). I will determine changes in IRAK1 mRNA levels and immune
cell profiles in blood and tracheal aspirate, and measure lung mechanics using non-invasive oscillometry. The
analysis will test the relationship of mRNA and cytokine levels and immune cell population with lung function and
echocardiogram.
Specific Aim 2: To test the hypothesis that newborn mice exposed to chorio have increased Th17 cell
activation via the IRAK1 pathway leading to long-term immune cell dysfunction and adverse lung
physiology. I will test if exposure to chorio alters pro-inflammatory cytokine concentrations and immune cell
populations in pups of wild type (WT) and IRAK1 KO mice. Lung mechanics will be tested by oscillometry, and
cardiac function assessed by echocardiography. Lungs will be harvested for histology, transcriptomic &
characterization of immune cell profile.

## Key facts

- **NIH application ID:** 10984592
- **Project number:** 1K08HL171892-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Viral G Jain
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $171,095
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984592

## Citation

> US National Institutes of Health, RePORTER application 10984592, IL17 mediates chorioamnionitis induced lung damage (1K08HL171892-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10984592. Licensed CC0.

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