# Exploring the biology of persistent type 2 airway niches in asthma

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $2,438,988

## Abstract

Summary / Abstract
This is a renewal application for a PPG that focuses on mechanisms of persistence of type 2 inflammation in
asthma. The central theme of our PPG is that the focal nature of type 2 inflammation that occurs in asthma
reflects the development of persistent “type 2 airway niches” that are characterized by epithelial cell and immune
cell reprogramming and mucus plug formation. Normal homeostatic responses to aeroallergens and other
inhaled insults include communications between epithelial cells and innate cells to recruit adaptive cells that limit
type 2 immune responses and restore airway function. When these repair mechanisms fail the normal airway
immune program is replaced by adaptive responses that favor persistence of airway type 2 inflammation and
formation of mucus plugs. This persistent and “ultra high” type 2 inflammation occurs in focal regions of the
asthma lung, as evidenced by our recent finding of focal and persistent eosinophilic mucus plugs in lung images
from patients with asthma. Our PPG will explore the biology of these focal type 2 airway niches in three
overarching aims. AIM 1 will determine how innate and adaptive immune cells in the persistent airway type 2
niche are reprogrammed to sustain inflammation. AIM 2 will determine how airway epithelial cells are
reprogrammed in type 2 niches to sustain inflammation. AIM 3 will determine how epithelial cells and eosinophils
sustain mucus gel pathology in type 2 airway niches. Our PPG comprises three projects led by multidisciplinary
teams of clinical scientists, immunologists and cell biologists. The projects are supported by three cores -
administration, human subjects, and biospecimens and bioinformatics. Our PPG proposes innovative concepts
for the pathogenesis of type 2-high asthma and it will deploy powerful and cutting edge technologies in the
experimental approaches that address our program aims. We are united in our ambition to aim for discoveries
that have the potential to lead to curative treatments for type 2-high asthma.

## Key facts

- **NIH application ID:** 10472526
- **Project number:** 5P01HL107202-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** John V Fahy
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,438,988
- **Award type:** 5
- **Project period:** 2012-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472526

## Citation

> US National Institutes of Health, RePORTER application 10472526, Exploring the biology of persistent type 2 airway niches in asthma (5P01HL107202-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10472526. Licensed CC0.

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