American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2015
Regulatory T Cell Impairment in Cystic Fibrosis Patients with Chronic Pseudomonas Infection.
Patients with cystic fibrosis (CF) lung disease have chronic airway inflammation driven by disrupted balance of T-cell (Th17 and Th2) responses. Regulatory T cells (Tregs) dampen T-cell activation, but their role in CF is incompletely understood. ⋯ Patients with CF who have chronic P. aeruginosa infection show an age-dependent, quantitative, and qualitative impairment of Tregs. Modulation of Tregs represents a novel strategy to rebalance T-cell responses, dampen inflammation, and ultimately improve outcomes for patients with infective CF lung disease.
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Am. J. Respir. Crit. Care Med. · Apr 2015
Hypoxic Epithelial Necrosis Triggers Neutrophilic Inflammation via IL-1 Receptor Signaling in Cystic Fibrosis Lung Disease.
In many organs, hypoxic cell death triggers sterile neutrophilic inflammation via IL-1R signaling. Although hypoxia is common in airways from patients with cystic fibrosis (CF), its role in neutrophilic inflammation remains unknown. We recently demonstrated that hypoxic epithelial necrosis caused by airway mucus obstruction precedes neutrophilic inflammation in Scnn1b-transgenic (Scnn1b-Tg) mice with CF-like lung disease. ⋯ Our results support an important role of hypoxic epithelial necrosis in the pathogenesis of neutrophilic inflammation independent of bacterial infection and suggest IL-1R as a novel target for antiinflammatory therapy in CF and potentially other mucoobstructive airway diseases.