Neutrophil Plasticity in Airway Disease: Balancing Damage and Repair

BACKGROUND: Neutrophils, previously viewed as short-lived microbial killers, are now recognized as highly adaptable regulators of innate immunity. Advances in transcriptomic, metabolic, and epigenetic profiling reveal their remarkable heterogeneity and ability to adopt microenvironment-specific phenotypes. In the lung, this plasticity gives neutrophils a double role: they fight infection but can also cause long-lasting inflammation, tissue damage, and scarring. SUMMARY: We review how neutrophils are activated, move, and act in lung disease, focusing on their release of proteases, production of reactive oxygen species, and formation of extracellular traps. We also describe repair-promoting neutrophil types and treatments that aim to reduce damage while keeping normal neutrophil defense intact. KEY MESSAGES: Learning how neutrophils change within the lung microenvironment will help create better and more precise treatments for lung inflammation and tissue damage.