ArticleScience translational medicine2012
NADPH oxidase inhibits the pathogenesis of systemic lupus erythematosus.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 231 citations in OpenAlex.
- Characteristics and Role of Neutrophil Extracellular Traps in Asthma.Inflammation · 2022Pooled it
- Diverse Roles of NETosis in the Pathogenesis of Lupus.Frontiers in immunology · 2022Pooled it
- 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
- Molecular Mechanisms of Negative Effect of Systemic Lupus Erythematosus on Oogenesis and Meiotic Processes in Oocytes.International journal of molecular sciences · 2026Review
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.Genome biology · 2025Article
- Neutrophil Extracellular Traps (NETs) in health and disease.Molecular biomedicine · 2025Review
- Neutrophil extracellular traps induced by Haemonchus contortus excretory-secretory proteins varies among goats, gerbils, and mice.Parasites & vectors · 2025Article
- The Role of NADPH Oxidase 2 in Leukocytes.Antioxidants (Basel, Switzerland) · 2025Review
- Sepsis-induced NET formation requires MYD88 but is independent of GSDMD and PAD4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Innate Immunity Reimagined: Metabolic Reprogramming as a Gateway to Novel Therapeutics.International journal of biological sciences · 2025Review
- Local Drug Delivery Systems as Novel Approach for Controlling NETosis in Periodontitis.Pharmaceutics · 2024Review
- NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7.JCI insight · 2024Article
- NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.The Journal of experimental medicine · 2024Article
- Reducing Abdominal Aortic Aneurysm Progression by Blocking Neutrophil Extracellular Traps Depends on Thrombus Formation.JACC. Basic to translational science · 2024Article
- Exploring the ROS reduction strategies in chronic lupus management.Frontiers in immunology · 2024Article
- How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease.International journal of molecular sciences · 2023Review
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Systemic Lupus Erythematosus and Antiphospholipid Syndrome.International journal of molecular sciences · 2023Article
- Article
85 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self nucleic acids. The source of autoantigen that drives disease onset and progression is unclear. A candidate source of autoantigen is the neutrophil extracellular trap (NET), which releases nucleic acids into the extracellular environment, generating a structure composed of DNA coated with antimicrobial proteins. On the basis of in vitro and patient correlative studies, several groups have suggested that NETs may provide lupus autoantigens. The observation that NET release (NETosis) relies on activity of the phagocyte NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox2) in neutrophils of both humans and mice provided a genetic strategy to test this hypothesis in vivo. Therefore, we crossed an X-linked nox2 null allele onto the lupus-prone MRL.Fas(lpr) genetic background and assessed immune activation, autoantibody generation, and SLE pathology. Counter to the prevailing hypothesis, Nox2-deficient lupus-prone mice had markedly exacerbated lupus, including increased spleen weight, increased renal disease, and elevated and altered autoantibody profiles. Moreover, heterozygous female mice, which have Nox2 deficiency in 50% of neutrophils, also had exacerbated lupus and altered autoantibody patterns, suggesting that failure to undergo normal Nox2-dependent cell death may result in release of immunogenic self-constituents that stimulate lupus. Our results indicate that NETosis does not contribute to SLE in vivo; instead, Nox2 acts to inhibit disease pathogenesis, making this enzyme an important target for further study and a candidate for therapeutic intervention.
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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.