ArticleNature medicine2016
Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 974 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins
Who cites it
974 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,489 citations in OpenAlex.
- From empirical treatment to precision intervention: a multi-database bibliometric analysis of neuropsychiatric systemic lupus erythematosus (2006-2025).Frontiers in immunology · 2026Pooled it
- Complement-amplified thrombotic microangiopathy in systemic lupus erythematosus and lupus nephritis: a systematic review of 78 reported patients.Frontiers in immunology · 2026Pooled it
- NLR outperforms PLR in SLE diagnosis and prognosis: an AI-enhanced meta-analysis of 12 850 patients with ethnicity-specific cut-offs.Lupus science & medicine · 2025Pooled it
- Therapeutic potential of extracellular vesicles in systemic lupus erythematosus: a systematic review.Immunologic research · 2025Pooled it
- NET-derived DNA is associated with cGAS-STING and type I IFN responses, as supported by monocyte stimulation cultures using plasma from female patients with SLE.EBioMedicine · 2026Article
- Disease modification in lupus nephritis: towards a pathophysiology-based treatment paradigm.Nature reviews. Nephrology · 2026Review
- Review
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- The Role of Neutrophil Extracellular Traps (NETosis) in Systemic Lupus Erythematosus: Molecular Mechanisms, Pathogenic Roles, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- The emerging roles of disulfidptosis in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
- Basophil Extracellular Traps in Immunity and Disease.Cancers · 2026Review
- Review
- ACSL1 orchestrates ferroptosis and degranulation in low-density neutrophils: a novel pathogenic mechanism and therapeutic target in systemic lupus erythematosus.Molecular and cellular biochemistry · 2026Article
- Mechanical stress promotes excessive NETs and exacerbates acute lung injury via Piezo1-mediated mitochondrial dysfunction.Redox biology · 2026Article
- Adventitial root extract of oplopanax elatus alleviates rheumatoid arthritis via inhibiting NETosis.Clinical rheumatology · 2026Article
- Rethinking the origins and functions of adaptive immunity.Trends in immunology · 2026Review
- A skin-kidney neutrophil axis links ultraviolet exposure to renal angiogenesis and tissue remodeling in healthy and lupus kidneys.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
914 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.