# Epithelial activation of airway inflammation in patients with non-T2 asthma

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2024 · $407,210

## Abstract

Project 2 Summary
Therapies for asthma that target type-2 (T2) inflammation are ineffective in many patients with asthma in part
due to the increasing number of individuals with non-T2 asthma who have a suboptimal response to standard
therapy with inhaled corticosteroids or biologics targeting T2 cytokines. Millions of viral-triggered asthma
exacerbations occur annually in this group of patients in the U.S. leading to significant morbidity and cost to the
health care system, due in part to the lack of effective treatments for non-T2 asthma for children and adults.
The clinical features and airway inflammatory cell infiltrate patterns of non-T2 asthma have been characterized
in detail, but the specific role of the airway epithelium in coordinating immune cell responses and influencing
exacerbations, lung function, and persistent inflammation in donors with non-T2 asthma remains poorly
characterized. Our preliminary studies demonstrate that airway epithelial cells (AECs) from non-T2 asthmatic
children exhibit more robust type I and III interferon (IFN) responses and greater “non-T2 cytokine” (IL-1β,
TNF-α, IL-17C, and GCSF) production following RV infection as compared to AECs from T2-high donors. In
Project 2, we will use bronchial AECs from well characterized cohorts of children and adults with and without
asthma to conduct mechanistic ex vivo experiments using organotypic models, to test our central hypothesis
that in non-T2 asthma RV infection triggers excessive epithelial production of non-T2 cytokines and/or
excessive IFN responses that activate the NLRP3 inflammasome, leading to neutrophilic inflammation, airway
remodeling, and lung function decline through interactions with Th17 cells and/or lung macrophages. We will
extend our ex vivo AEC model to include coculture studies of AECs with both Th17 and lung macrophages,
and specifically assess bidirectional interactions utilizing bulk and single cell transcriptomics to assess
epithelial-dependent neutrophil activation. We will also utilize cutting edge bioinformatics techniques to assess
the genomic and epigenetic alterations in the epithelium that drive non-T2 inflammation as well as relevant in
vivo modeling of HRV infection in the setting of non-T2 inflammation.

## Key facts

- **NIH application ID:** 10832571
- **Project number:** 5U19AI175089-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JASON S DEBLEY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $407,210
- **Award type:** 5
- **Project period:** 2023-04-25 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832571

## Citation

> US National Institutes of Health, RePORTER application 10832571, Epithelial activation of airway inflammation in patients with non-T2 asthma (5U19AI175089-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10832571. Licensed CC0.

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