ArticleRespiratory research2025
Neutrophil extracellular traps (NETs) are increased in rheumatoid arthritis-associated interstitial lung disease.
Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- From immunological mechanisms to targeted therapies: a bibliometric analysis in the domain of research concerning neutrophil extracellular traps and pulmonary diseases (2006-2025).Frontiers in immunology · 2026Pooled it
- Neutrophils have altered response to acute respiratory viral infection in sputum of patients with rheumatoid arthritis.The journal of allergy and clinical immunology. Global · 2026Article
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Sex-specific COX-2/CREB/ER signaling underlies male susceptibility to pulmonary fibrosis in rheumatoid arthritis-associated interstitial lung disease.Frontiers in immunology · 2026Article
- Inflammatory responses driven by neutrophil extracellular traps in cardiovascular diseases: molecular mechanisms, emerging biomarkers, and therapeutic targets.Frontiers in immunology · 2026Review
- Roles of immune cell metabolism in rheumatoid arthritis.Frontiers in immunology · 2026Review
- Multifactorial pathogenesis of rheumatoid arthritis: interaction between inflammation, metabolic dysregulation, and tissue mechanics.Frontiers in immunology · 2026Review
- Toward targeting of inflammasome signaling in venous thrombosis.Journal of thrombosis and haemostasis : JTH · 2025Review
- Breaking the cycle: should we target inflammation, fibrosis, or both?Frontiers in immunology · 2025Review
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
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8 authors.
Funding
Abstract
backgroundNeutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms.
methodsSingle-cell sequencing was used to identify changes in the quantity and function of neutrophils in the lung tissue of a zymosan A (ZYM)-induced interstitial pneumonia arthritis model. Additionally, nuclear receptor 4A3 (NR4A3) interference was performed in HL-60 cells to assess its impact on NET formation and the transformation of MRC-5 cells into myofibroblasts. The clinical relevance of plasma myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (Cit-H3), and cell-free DNA was evaluated in RA-ILD patients with different imaging types via a commercial enzyme-linked immunosorbent assay (ELISA).
resultsIn the ZYM-treated SKG mouse model, which recapitulates key features of RA-ILD, an increased population of neutrophils in the lung tissue was primarily responsible for NET formation. Mechanistically, we found that interference with NR4A3 expression enhanced NET formation in HL-60 cells, which in turn promoted the differentiation of MRC-5 cells into myofibroblasts. Clinically, plasma MPO-DNA levels are elevated in patients with RA-nonspecific interstitial pneumonia (RA-NSIP), whereas Cit-H3 levels are elevated in RA-usual interstitial pneumonia (RA-UIP) patients compared with healthy subjects. ROC curve analysis further revealed that the combination of plasma MPO-DNA, rheumatoid factor (RF), and anti-citrullinated protein (anti-CCP) and the combination of Cit-H3, RF, and anti-CCP were superior diagnostic panels for NSIP and UIP in RA-ILD patients, respectively. Moreover, compared with those from healthy controls, neutrophils from patients with RA-UIP and RA-NSIP demonstrated a significantly increased ability to form NETs and induce the differentiation of MRC-5 cells into myofibroblasts. Specifically, RA-UIP patients exhibited a greater capacity for NET formation and the differentiation of MRC-5 cells into myofibroblasts than did RA-NSIP patients.
conclusionsThese findings suggest that targeting NETs may be a novel therapeutic approach for treating ILD in RA patients.
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