# Airway inflammation and airway remodeling - Project 2

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $354,001

## Abstract

Asthma can manifest with varying levels of severity. Whereas the acute phase of mild and moderate
asthma is characterized largely by rapid infiltration of a number of cell types within the lungs, such as T
lymphocytes, eosinophils, and mast cells, severe asthma has additional features that are thought to strongly
contribute to decline in lung function. These include airway epithelial cell mucus metaplasia, smooth muscle
hypertrophy or hyperplasia, subepithelial fibrosis, and increased angiogenesis. Fibrosis is due to deposition of
extracellular matrix proteins such as collagen, fibronectin, tenascin, and laminin, thought to be produced
largely by differentiating fibroblasts or epithelial cells. These structural cells can additionally be induced to
express alpha smooth muscle actin and may contribute to increased rigidity of the airways together with
proliferation or hypertrophy of mature smooth muscle cells that line the bronchioles. The inflammatory factors
that control all of these cell types are then likely to be important in severe asthma. This proposal will focus on
several members of the tumor necrosis factor (TNF) and TNF receptor superfamily, and test the hypotheses
that LIGHT (TNFSF14) interacting with its two receptors HVEM (TNFRSF14) and LTR (TNFRSF3), and TL1A
(TNFSF15) interacting with its receptor DR3 (TNFRSF25), are central mediators and drivers of the fibrotic and
remodeling activities of lung epithelial cells, lung fibroblasts, and airway smooth muscle cells. The treatment
options for asthmatics are currently limited. Understanding when and where these TNF/TNFR family molecules
are expressed, and the functional response that is elicited from their interactions, might lead to new and novel
targets for therapeutic intervention in severe asthma.

## Key facts

- **NIH application ID:** 9993182
- **Project number:** 5U19AI070535-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Michael Croft
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,001
- **Award type:** 5
- **Project period:** 2006-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993182

## Citation

> US National Institutes of Health, RePORTER application 9993182, Airway inflammation and airway remodeling - Project 2 (5U19AI070535-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993182. Licensed CC0.

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