# Development of an animal model of severe neutrophilic asthma

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $78,000

## Abstract

PROJECT SUMMARY
The goal of this proposal is to establish an animal model for steroid-resistant neutrophilic asthma, that
replicates patient symptoms to understand the underlying cellular and molecular pathology. Asthma is a
chronic inflammatory disease characterized by recruitment of inflammatory cells, bronchial hyperreactivity,
mucus production, and airway remodeling and narrowing. According to Centers for Disease Control and
Prevention, 8.3% of the US population (children and adults) suffers from asthma with varying degree of
severity. It has commonly been considered that airway inflammation is caused by the Th2 immune response,
or eosinophilia, which is a hallmark of bronchial asthma pathogenesis. However, multiple clinical reports show
that as high as 50% patients with symptomatic asthma have elevated sputum neutrophil counts. This non-
eosinophilic asthma is often refractory to corticosteroids, the mainstay of asthma treatment, and is strongly
associated with the presence of Th17 cytokines in the bronchial tissues and sputum. The clinical pattern of
neutrophilic asthma is different from eosinophilic asthma with evidence of abnormal upper airway responses.
Currently, the molecular pathology underlying neutrophilic asthma is very poorly understood, mainly due to the
lack of appropriate animal models. Due to its alarmingly high prevalence, there is an urgent need to
understand the pathophysiology of neutrophilic asthma, to inform targeted therapy. T cells from diverse
individuals show different propensity to differentiate into distinct effector lineages, which underscores their
susceptibility to allergic and inflammatory diseases. Genome-wide association studies on human subjects
provide valuable information about intrinsic factors governing T cell responses, but these results are highly
influenced by various environmental factors including weather and diet. To minimize influence of environmental
factors, we examined cytokine expressions in T cells isolated from a hybrid mouse diversity panel consisting of
107 common inbred and recombinant-inbred strains fed with the same diet and housed under specific
pathogen-free conditions. These efforts have resulted in identification of mouse strains that all show strong Th2
responses, but have varying degree of Th17 responses. Based on our findings, our specific goals are to 1)
develop a new animal model of neutrophilic asthma using the mouse strain with T cells that shows high
propensity to both Th2 and Th17 differentiation and 2) determine the cellular and molecular mechanism
underlying propensity to neutrophilic asthma in these mice.

## Key facts

- **NIH application ID:** 9964664
- **Project number:** 5R03AI147063-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Yousang Gwack
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964664

## Citation

> US National Institutes of Health, RePORTER application 9964664, Development of an animal model of severe neutrophilic asthma (5R03AI147063-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964664. Licensed CC0.

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