ArticleArthritis & rheumatology (Hoboken, N.J.)2017
Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- The systemic lupus erythematosus-associated NCF1Nature communications · 2025Article
- NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7.JCI insight · 2024Article
- Redox Pathogenesis in Rheumatic Diseases.ACR open rheumatology · 2024Review
- NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.The Journal of experimental medicine · 2024Article
- Evaluation of NADPH Oxidase (NOX) Activity by nitro Blue Tetrazolium (NBT) Test in SLE Patients.Mediterranean journal of rheumatology · 2023Article
- Myeloid cell MHC I expression drives CD8Frontiers in immunology · 2023Article
- Anti-Inflammatory Neutrophil Functions in the Resolution of Inflammation and Tissue Repair.Cells · 2022Review
- Neutrophil and Macrophage NADPH Oxidase 2 Differentially Control Responses to Inflammation and to Aspergillus fumigatus in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells.The Journal of clinical investigation · 2022Article
- Article
- Regulatory strategies limiting endosomal Toll-like receptor activation in B cells.Immunological reviews · 2022Review
- Rubicon promotes rather than restricts murine lupus and is not required for LC3-associated phagocytosis.JCI insight · 2022Article
- Redox Homeostasis Involvement in the Pharmacological Effects of Metformin in Systemic Lupus Erythematosus.Antioxidants & redox signaling · 2022Review
- Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile-onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children.Molecular genetics & genomic medicine · 2022Article
- Immunogenetics of Lupus Erythematosus.Advances in experimental medicine and biology · 2022Article
- NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE.JCI insight · 2021Article
- A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection.eLife · 2021Article
- Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?Frontiers in immunology · 2021Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveWe have previously established that the gene for neutrophil cytosolic factor 2 (NCF-2) predisposes to lupus, and we have identified lupus patients with point mutations that are predicted to cause reduced NADPH oxidase activity. We undertook this study to investigate the relationship between reduced leukocyte NADPH oxidase activity and immune dysregulation associated with systemic lupus erythematosus (SLE).
methodsWe generated NCF-2-null mice, in which NADPH oxidase activity is absent, on the nonautoimmune C57BL/6 (B6) mouse background and on the NZM 2328 mouse background, a polygenic model in which mice spontaneously develop lupus. Clinical disease, serology, and immunopathology were evaluated.
resultsNCF-2-null mice on the B6 background were susceptible to Aspergillus fumigatus pneumonia characteristic of chronic granulomatous disease, but did not develop systemic lupus disease. In contrast, NCF-2-null and even NCF-2-haploinsufficient mice on the NZM 2328 background developed accelerated full-blown lupus with significantly accelerated lupus kidney disease. This was characterized by more rapid development of hyperactive B cell and T cell immune compartments, increased expression of type I interferon-responsive genes, and generation of neutrophil extracellular traps, which were observed even in the absence of NADPH oxidase activity.
conclusionJust as patients with chronic granulomatous disease who lack NADPH oxidase rarely develop SLE, NCF-2-null mice on a nonautoimmune background were susceptible to a chronic granulomatous disease-like opportunistic infection but did not develop lupus. In contrast, on a lupus-prone background, even haploinsufficiency of NCF-2 accelerated the development of full-blown lupus disease. This establishes an interaction between reduced oxidase activity and other lupus-predisposing genes, paralleling human SLE-associated variants predicted to have only reduced NADPH oxidase activity.
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