# Lung repair mechanisms mediated by the immune-fibroblast interface

> **NIH NIH R35** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $445,000

## Abstract

PROJECT SUMMARY
The pulmonary mesenchyme, which includes fibroblasts and smooth muscle, provides critical support for
resident epithelial progenitors, but how it contributes to lung injury resolution is unclear. As a barrier organ the
lung is constantly exposed to inhaled particulates, allergens, and respiratory pathogens. This barrage of
exposures is countered by mucous secretions, antimicrobial agents, and sentinel immune cells. In the case of a
more severe insult that causes lung damage, the inflammatory response and activation of wound-healing
fibroblasts ensues. The research program described here seeks to elucidate how signaling between resident
fibroblasts and immune cells controls the length and successful outcome of the lung injury repair response.
Further, this research will test a new model proposed for the origins of human lung disease by testing how
dysfunctional epithelial cells perpetuate the inflammation-driven fibroblast response. The overarching goal of this
program is to determine the molecular pathways utilized by distinct fibroblast subsets and how they converge to
shape the immune status of the lung. These questions will be explored by using our unique genetic mouse
models for fibroblast lineages and in vivo models of respiratory dysfunction including chemical-induced injury or
influenza infection. Moreover, we propose to employ a combination of sequencing analysis and establish novel
organoid models to explore the interactions of fibroblast subsets and tissue resident immune cells. Together, our
efforts will provide new insights in the mechanisms of lung repair resolution and build a foundation for novel
future contributions.

## Key facts

- **NIH application ID:** 10876267
- **Project number:** 5R35GM146835-03
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Jarod Zepp
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,000
- **Award type:** 5
- **Project period:** 2022-09-05 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876267

## Citation

> US National Institutes of Health, RePORTER application 10876267, Lung repair mechanisms mediated by the immune-fibroblast interface (5R35GM146835-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876267. Licensed CC0.

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