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

## TL;DR

This paper explores how neutrophil extracellular traps contribute to pulmonary fibrosis and how targeting them could lead to better treatments.

## Contribution

The paper systematically reviews NETosis pathways and therapeutic strategies specific to pulmonary fibrosis subtypes.

## Key findings

- NETs mediate inflammation-to-fibrosis transition and immune crosstalk in pulmonary fibrosis.
- Three NET-targeted therapies differ in subtype adaptability and clinical transformation challenges.
- Subtype-specific NET mechanisms reveal potential for precision medicine in pulmonary fibrosis.

## Abstract

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.