{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:46:02Z","timestamp":1792856762674,"version":"4.5.0"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1765590","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:42:44Z","timestamp":1772602964000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Neutrophil extracellular traps in pulmonary fibrosis: mechanisms, immunity and therapeutic targets"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pathology, Basic Medical School, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xiangya Hospital, Xiangya School of Basic Medical Sciences, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2005230","article-title":"Spectrum of fibrotic lung diseases","volume":"383","author":"Wijsenbeek","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2103187","DOI":"10.1183\/13993003.03187-2021","article-title":"Progressive pulmonary fibrosis: an expert group consensus statement","volume":"61","author":"Rajan","year":"2023","journal-title":"Eur Respir J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e744","DOI":"10.1002\/mco2.744","article-title":"Pulmonary fibrosis: pathogenesis and therapeutic strategies","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"B5","doi-asserted-by":"publisher","first-page":"10001","DOI":"10.70322\/jrbtm.2025.10001","article-title":"Mechanisms and therapeutic potential of myofibroblast transformation in pulmonary fibrosis","volume":"2","author":"Zhao","year":"2025","journal-title":"J Respir Biol Transl Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/cells10040897","article-title":"The role of macrophages in the development of acute and chronic inflammatory lung diseases","volume":"10","author":"Lee","year":"2021","journal-title":"Cells"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1296890","article-title":"Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment","volume":"11","author":"Althobiani","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1186\/s12889-023-16295-2","article-title":"Global incidence, prevalence and disease burden of silicosis: 30 years\u2019 overview and forecasted trends","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Public Health"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-022-02395-9","article-title":"What do we need to know about rising rates of idiopathic pulmonary fibrosis? 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