# Genetic targeting of intraepithelial mast cells

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $256,650

## Abstract

Project Summary/Abstract:
Mast cells (MCs) expand within the airway epithelium during prevalent and burdensome human respiratory
disease, including asthma and nasal polyposis, where they are thought to play a central role in disease
pathobiology. The expanded intraepithelial MC compartment characteristic of Th2 high asthma correlates with
disease severity and therapeutic targeting of this compartment improves patient outcomes, suggesting a
central role in disease pathobiology. Despite this, the mechanism(s) through which intraepithelial mast cells
participate in airway inflammation remain unclear, in part due to a lack of robust pre-clinical models to
selectively target this MC subset in an in-vivo setting. This proposal describes the creation of a novel mouse
strain in which tamoxifen-inducible cre recombinase coupled with a fluorescent reporter tag is selectively
expressed within the lung by inflammation-expanded intraepithelial mast cells, termed mucosal mast cells
(MMCs) in mice, and will use this strain to test the hypothesis that intraepithelial mast cells are an important
contributor to airway inflammatory disease progression. Aim 1 of this study will validate reporter construct
restriction to the MMC lineage across tissues and conduct a timecourse analysis of the dynamics of construct
upregulation and its long-term maintenance within the lung MMCs compartment. Aim 2 will use our strain to
generate inducible MMC knockout mice, which will then be used to test the degree to which MMC regulate
pulmonary inflammation and airway hyperreactivity at two discrete phases of allergic lung inflammation.
Completion of these aims will provide definitive evidence as to the importance of MMC in allergic lung
inflammation and set the stage for future studies using this strain to both determine the mechanism(s) through
which they influence lung inflammation and test their importance in other models of mucosal inflammation,
such as food allergy and eosinophilic esophagitis.

## Key facts

- **NIH application ID:** 10947468
- **Project number:** 1R21AI186023-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Daniel F Dwyer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $256,650
- **Award type:** 1
- **Project period:** 2024-05-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947468

## Citation

> US National Institutes of Health, RePORTER application 10947468, Genetic targeting of intraepithelial mast cells (1R21AI186023-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10947468. Licensed CC0.

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