# Innate Immune Defect and Neutrophilic Inflammation in Cystic Fibrosis

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $377,074

## Abstract

ABSTRACT
 Cystic fibrosis (CF) is one of the most common and deadly genetic disorders, affecting ~1/3,000 live births
in the United States. The responsible genetic mutations are linked to the gene that encodes CF
Transmembrane-conductance Regulator (CFTR), a cAMP-activated chloride channel. Although this disease
affects almost all organs and systems, its lung complications claim the most morbidity and mortality. The
prominent lung pathology is marked by chronic bacterial infection, persistent neutrophilic inflammation, and
purulent small airway obstruction, of which persistent lung inflammation is responsible for lung structure
damage and function loss. Even though the CF molecular defect was discovered three decades ago, the link
between the CFTR chloride channel defect and the destructive lung inflammation has not been defined. Such a
knowledge gap impedes any informed development of effective therapies for CF. The current proposal is to
address this outstanding problem in the field. Our overarching hypothesis is that CFTR loss-of-function in
marrow-derived innate immune cells compromises their ability to molecularly modify and functionally deactivate
inflammatory agonists, leading to excessive stimulation and neutrophilic inflammation in CF lungs. To test this
hypothesis, we propose three specific aims: Aim 1: Determine that lineage-specific CFTR loss-of-function in
neutrophils and monocytes/macrophages leads to persistent neutrophilic inflammation in the lung differentially;
Aim 2: Determine that CF lung neutrophilic inflammation is due to neutrophil excessive recruitment, reduced
apoptosis, and/or inefficient efferocytosis; Aim 3: Define that CF neutrophils and macrophages are
compromised in chemical modification and functional deactivation of neutrophil chemotactic factors.
Completion of this research will provide novel insights into CF lung disease pathogenesis. The new knowledge
obtained will guide the rational design of interventions for effective treatment of this devastating disease.

## Key facts

- **NIH application ID:** 10052074
- **Project number:** 1R01HL150370-01A1
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** GUOSHUN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,074
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052074

## Citation

> US National Institutes of Health, RePORTER application 10052074, Innate Immune Defect and Neutrophilic Inflammation in Cystic Fibrosis (1R01HL150370-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052074. Licensed CC0.

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