Neutrophil extracellular traps in pulmonary fibrosis: mechanisms, immunity and therapeutic targets

Pulmonary fibrosis, a heterogeneous and fatal interstitial lung disease, lacks curative therapies and specific biomarkers, posing great clinical challenges. Neutrophil extracellular traps (NETs) are key inflammatory mediators in pulmonary fibrosis pathogenesis, yet subtype-specific regulatory mechanisms and targeted therapeutic optimization remain unclear. This review systematically elucidates the distinct NETosis pathways across various subtypes. We further elaborate the multi-layered mechanisms of NETs in mediating inflammation-fibrosis transition, fibroblast activation, and innate-adaptive immune crosstalk, revealing subtype-specific pathological effects of NETs in pulmonary fibrosis. Additionally, we conduct a critical comparison of three NET-targeted therapeutic strategies and their advantages, limitations as well as subtype adaptability. Finally, we summarize the clinical transformation challenges of NET-targeted therapies and propose optimization directions. This review provides a precise theoretical framework for understanding PF immunopathogenesis and offers actionable insights for advancing NET-targeted precision medicine in pulmonary fibrosis.