REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
This article is part of the Research TopicNeutrophil function and dysfunction: Pathways, impact, and therapeutic insightsView all 5 articles
Neutrophils as Key Drivers of Pulmonary Fibrosis: Unveiling Mechanisms and Therapeutic Implications
Provisionally accepted
- 1Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
- 2West China Hospital, Sichuan University, Chengdu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Pulmonary fibrosis is a chronic interstitial lung disease with an incompletely understood pathogenesis, and currently, effective treatment strategies remain elusive. Neutrophils, as pivotal effector cells of the innate immune system, are integral to the progression of pulmonary fibrosis. This review systematically examines the mechanisms by which neutrophils contribute to the advancement of pulmonary fibrosis through tissue infiltration, the release of neutrophil elastase (NE), and the formation of neutrophil extracellular traps (NETs). The interactions between neutrophils and other cell types, including alveolar macrophages, epithelial cells, and fibroblasts, create a complex inflammatory and fibrotic network. Clinical studies suggest that neutrophil levels and associated biomarkers, such as NET components, may serve as valuable indicators for disease assessment. Targeted therapeutic strategies, such as NE inhibitors, peptidyl arginine deiminase 4 (PAD4) inhibitors, blockade of the C5a-C5aR1 axis, and stem cell therapy, present promising avenues for the treatment of pulmonary fibrosis. This article aims to provide a comprehensive overview of the multifaceted roles of neutrophils in pulmonary fibrosis and their therapeutic implications.
Keywords: Pulmonary Fibrosis, Neutrophils, neutrophil extracellular traps, Neutrophil Elastase, crosstalk
Received: 03 Oct 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Liang, Yanhong, Tang, Luo and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yi Liu, yiliu8999@wchscu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.