# Mapping Airway Epithelial Cell-Immune Cell Interactions in Lung Health and Disease

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $798,062

## Abstract

Project Summary
Asthma and chronic obstructive pulmonary disease (COPD) are inflammatory diseases that affect the airways
and, together, are the largest causes of disability and mortality from chronic respiratory disorders worldwide. At
the heart of the pathophysiology of both diseases is altered airway epithelial cell (AEC)-immune cell interactions
with aberrant activation of innate and adaptive immunity, notable for the accumulation of activated airway T cells
and B cells. It is thought that pathogenic AEC-myeloid cell-CD4+ T cell circuits underlie the pathophysiology of
asthma, while AEC-myeloid cell-CD8+ T cell circuits predominate in COPD, but the diversity of AECs and immune
cells involved are only now receiving scrutiny. In particular, rare AEC subtypes, including tuft, hillock, microfold,
and neuroendocrine cells, are known to secrete immune cell-active mediators, but their role in human disease
has not been established. Additionally, airway cellular structures such as hillock islands and inducible bronchial
associated lymphoid tissue (iBALT) are immunologically active in asthma and COPD, but their role in disease
pathogenesis is unknown. Furthermore, studies suggest that the T cell and B cell response to specific antigens,
whether host-, allergen- and/or microbe-derived, may be important in the pathophysiology of asthma and COPD,
but current efforts have not deeply characterized the specificity and function of the adaptive immune cells that
accumulate in airways, nor their interactions with specific AEC populations. Our overall objective is to
comprehensively define the signaling and spatial relationships of common and rare AEC cell types, airway
structures such as the hillock and iBALT, and specific airway immune cell populations in asthma and COPD to
ultimately define therapeutic approaches that precisely target disease-specific mechanisms. Our group has
established protocols and methods for safely sampling asthmatic and COPD airways from well-defined patient
cohorts and for obtaining tissue from diseased lung explants and donor lungs with asthma that were rejected for
transplants. Using these methods, we have characterized the cellular profiles of AEC and immune cells in
healthy, asthmatic, and COPD lungs and have defined some of the critical AEC-immune cell interactions within
the airways of these subjects. We hypothesize that aberrant AEC-immune cell interactions involving AEC
subtypes as well as airway structural features such as hillock islands and iBALT drive chronic immune activation
in the airway, which ultimately promotes activation of airway-resident memory T cells and B cells, thus
establishing a persistent inflammatory state that shapes the clinical course of asthma and COPD. The specific
aims are 1) to determine and compare the transcriptional and spatial profiles of AEC-immune cell interactions in
asthma and COPD, and 2) to define T cell and B cell receptor repertoires in the airways of patients with asthma
and COPD. A de...

## Key facts

- **NIH application ID:** 10974664
- **Project number:** 1U01HL175384-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jacques Deguine
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $798,062
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974664

## Citation

> US National Institutes of Health, RePORTER application 10974664, Mapping Airway Epithelial Cell-Immune Cell Interactions in Lung Health and Disease (1U01HL175384-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10974664. Licensed CC0.

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