# Airway Dendritic Cells in the Allergic Asthma Phenotype

> **NIH NIH UH2** · UNIVERSITY OF IOWA · 2020 · $233,872

## Abstract

Project Summary
Asthma affects more than 300 million individuals worldwide, and more than half of patients with asthma have
inadequately controlled symptoms and frequent exacerbations. Advances in our understanding of the
immunology of asthma have led to the development of targeted biologic therapies against a single cytokine or
receptor. Although these targeted therapies reduce exacerbations, they have not demonstrated disease
modifying effects. Most asthma is allergic in origin, and the strongest risk factor for allergic asthma is allergy. Not
all allergic patients have asthma, but many develop the disease over time, suggesting there are incremental and
potentially reversible stages in the development of allergic asthma. Thus, identification of differences between
allergic asthmatics (AA) and allergic non-asthmatic controls (AC) may provide insight into the mechanisms that
ultimately lead to the development of asthma. The long-term goal of this research is to determine how dendritic
cells (DC) orchestrate secondary immune responses in the lung and ultimately identify novel therapeutic targets
aimed at inducing asthma remission. DC are critical regulators of the effector T cell response in the lung mucosa,
and our previously published data suggest there are key differences in re-activation of allergen-specific T helper
type 2 (Th2) cells during secondary responses in the lung. Therefore, we hypothesize that differences in airway
DC between AA and AC determine the asthma phenotype. For this proposal, we will utilize bronchoscopic
segmental allergen challenge (SAC) to mimic an asthma exacerbation in AA and AC and compare the immune
response in the airway. Our preliminary data suggests that a subset of conventional DC in the bronchoalveolar
lavage (BAL) may be more activated at baseline in AA compared to AC and that AA have higher levels of Th2-
type cytokines and IgE in the airways following SAC. Furthermore, DC in AA may accumulate in the airway
mucosa after allergen challenge. Finally, we demonstrate that the airway mucosa may be a separate immune
microenvironment and identify the cellular components of inducible bronchus associated lymphoid tissue (iBALT)
in mucosal samples. Based on these data we propose: Aim #1 to compare the phenotype of airway mucosal
DC and BAL DC in AA and AC and Aim #2 to determine the transcriptional identity of airway mucosal immune
cells in AA and AC. In Aim #1, we will compare the phenotype of DC isolated from BAL and the airway mucosa
(using endobronchial brushing) of AA and AC at baseline and after SAC. We will also assess for known mediators
of iBALT formation. In Aim #2, we will perform a comprehensive, unbiased transcriptional analysis of the immune
cells in the airway mucosa using single-cell RNA sequencing (scRNAseq). We will also obtain endobronchial
biopsies to assess for the presence of organized iBALT and validate the findings from scRNAseq. We believe
these studies will advance our understanding of asthma...

## Key facts

- **NIH application ID:** 9917696
- **Project number:** 5UH2AI144434-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Josalyn L Cho
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $233,872
- **Award type:** 5
- **Project period:** 2019-04-18 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917696

## Citation

> US National Institutes of Health, RePORTER application 9917696, Airway Dendritic Cells in the Allergic Asthma Phenotype (5UH2AI144434-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9917696. Licensed CC0.

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