# Regulatory T cells and Inflammatory Injury of the Developing Murine Lungs

> **NIH NIH R03** · BAYLOR COLLEGE OF MEDICINE · 2021 · $80,000

## Abstract

Abstract/Summary
 Bronchopulmonary dysplasia (BPD) is the most common chronic infantile lung disease that lacks
curative therapies. Further, BPD increases the economic burden and long-term morbidities in preterm infants.
Sepsis-mediated persistent lung inflammation is central to the pathogenesis of BPD, which is characterized by
interrupted lung development, i.e., alveolar simplification. However, the molecular mechanisms that modulate
neonatal lung inflammation are poorly understood. Regulatory T cells (Tregs) are crucial to maintain immune
homeostasis and prevent tissue damage. Further, they promote resolution of lung inflammation and injury in
adult animals; however, the role of Tregs in BPD pathogenesis remains unclear. Additionally, the mechanisms
of Treg recruitment in neonatal lungs are poorly studied. So, we propose to address these knowledge gaps
using a neonatal mouse model of lipopolysaccharide (LPS)-induced chronic inflammatory lung injury. Our
preliminary studies in neonatal mice indicate that: (1) LPS decreases Tregs and their C-C motif chemokine
receptor 5 (CCR5) expression in lungs; and (2) Treg depletion induces inflammation and potentiates LPS-
mediated lung injury. Based on our novel data, we will test the central hypothesis that Tregs are necessary and
sufficient to protect against LPS-induced inflammatory lung injury in neonatal mice. We will use a unique
combination of molecular, cellular, and functional approaches to test this hypothesis. In Aim 1, we will use
transgenic mice to determine if Tregs are necessary and sufficient to protect neonatal mice against LPS-
induced lung and pulmonary vascular injury and dysfunction. In Aim 2, we will use transgenic mice to examine
the mechanisms of lung Treg recruitment. We expect that successful completion of these studies would
provide a mechanistic rationale for targeting Tregs to develop meaningful therapies for BPD infants. Our
studies also could positively impact other inflammation-related neonatal research areas, including necrotizing
enterocolitis, retinopathy of prematurity, and periventricular leukomalacia.

## Key facts

- **NIH application ID:** 10109430
- **Project number:** 1R03HD103823-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Binoy Shivanna
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $80,000
- **Award type:** 1
- **Project period:** 2021-03-08 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109430

## Citation

> US National Institutes of Health, RePORTER application 10109430, Regulatory T cells and Inflammatory Injury of the Developing Murine Lungs (1R03HD103823-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10109430. Licensed CC0.

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