# Contribution of nerves and neuropeptides to inflammation in asthma

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $90,886

## Abstract

PROJECT SUMMARY/ABSTRACT
This project investigates the contribution of the pulmonary sensory afferent nervous system to airway
inflammation in asthma and its relationship to asthma endotypes. Asthma is a highly prevalent disease in
children and adults with that causes diminished quality of life, work/school absence, increased healthcare
utilization and associated costs, and in extreme cases, disability and even death. While all asthmatic patients
fulfill the same diagnostic criteria of intermittent wheeze, cough, and chest tightness in the presence of airflow
obstruction or bronchoprovocation testing with response to bronchodilating agents, it is now understood that
asthma represents a heterogenous set of distinct pathological phenotypes of asthma that produce the same
hallmark clinical syndrome (1). Using gene expression analysis from asthmatics and controls, the laboratory of
my mentor, Dr. Prescott Woodruff, has described two important endotypes of asthma involving TH2-high or
TH2-low genetic signatures. Given the variable response to available therapies for asthma between different
asthmatic phenotypes, new insights into the pathogenesis of known phenotypes and elucidation of novel
subphenotypes is of significant clinical importance. In recent years, a compelling body of work has emerged
that establishes immunomodulatory connections between neuropeptides secreted from airway nerves and
pulmonary neuroepithelial cells (PNECs) (2,3) and cells in the airway compartment, including epithelial cells,
resident innate lymphoid cells (ILCs), and infiltrating immune cells, among others. Several neuropeptides,
including Calcitonin Gene-Related Peptide (CGRP) and Vasoactive Intestinal Peptide (VIP), are implicated in
development of allergic asthma in animal models. Using already-gathered epithelial biopsies and BAL fluid
from asthmatic subjects and healthy controls, the experiments proposed in this application will investigate the
presence and role of the neuropeptides CGRP and VIP in promoting and/or maintaining TH2
inflammation in the asthmatic airway via interactions with epithelial cells, PNECs, ILC2 cells, and other
immune cells. My initial aim is to examine differences in nerve density, neuropeptide concentration in BALF,
and neuropeptide receptor expression within known asthma TH2-high and TH2-low endotypes, with a goal of
establishing specific neuropeptidergic phenotypes or sub-phenotypes in these patients. In my second aim, I
will analyze whether neuropeptidergic phenotypes are correlated with important clinical and biological
outcomes, including degree of airway obstruction, symptom burden, sputum and serum biomarker levels, and
exacerbation history, controlling for TH2 status. I expect that our findings will establish novel
neural/neuropeptide pathway-related phenotypes that may be amenable for precision-guided therapies aimed
at neurogenic inflammation in asthma.

## Key facts

- **NIH application ID:** 10235442
- **Project number:** 1F32HL158222-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** William McKleroy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $90,886
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235442

## Citation

> US National Institutes of Health, RePORTER application 10235442, Contribution of nerves and neuropeptides to inflammation in asthma (1F32HL158222-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10235442. Licensed CC0.

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