ArticleJCI insight2023
NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Review
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- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Macrophage retrotransposon expression is associated with lupus.Genes and immunity · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- Case Report: Severe neonatal lupus in an infant with homozygousFrontiers in immunology · 2026Article
- Plasmacytoid dendritic cells in systemic and cutaneous lupus erythematosus: an evolving understanding.Frontiers in immunology · 2026Review
- An Overview of the Pathogenesis of Cutaneous Lupus Erythematosus.Journal of clinical medicine · 2025Review
- Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Free Radicals in Health and Disease.MedComm · 2025Review
- The need for Cre-loci controls in conditional mouse experiments: Mrp8-cre transgene predisposes mice to antibody-induced arthritis.Genes and immunity · 2025Article
- The systemic lupus erythematosus-associated NCF1Nature communications · 2025Article
- Sarcoidosis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1Annals of the rheumatic diseases · 2025Article
- Whole-Exome Sequencing: Discovering Genetic Causes of Granulomatous Mastitis.International journal of molecular sciences · 2025Article
- Systemic lupus erythematosus: from an adverse event of interferon administration to a disease with new treatment options.Upsala journal of medical sciences · 2025Review
- Liangxue Qushi Zhiyang Decoction Inhibits Atopic Dermatitis in Mice via FcMediators of inflammation · 2025Article
- Cytokine-induced transcriptional changes in human neutrophils reveal immune regulatory plasticity.Discovery immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low capacity to produce ROS because of mutations in neutrophil cytosolic factor 1 (NCF1/p47phox), a component of NADPH oxidase 2 (NOX2) complex, is strongly associated with systemic lupus erythematosus in both humans and mouse models. Here, we aimed to identify the key immune cell type(s) and cellular mechanisms driving lupus pathogenesis under the condition of NCF1-dependent ROS deficiency. Using cell-specific Cre-deleter, human NCF1-339 variant knockin, and transgenic mouse strains, we show that low ROS production in plasmacytoid dendritic cells (pDCs) exacerbated both pristane-induced lupus and a potentially new Y-linked autoimmune accelerating locus-related spontaneous model by promoting pDC accumulation in multiple organs during lupus development, accompanied by elevated IFN-α levels and expression of IFN-stimulated genes. Mechanistic studies revealed that ROS deficiency enhanced pDC generation through the AKT/mTOR pathway and CCR2-mediated migration to tissues, which together with hyperactivation of the redox-sensitive stimulator of interferon genes/IFN-α/JAK1/STAT1 cascade further augmented type I IFN responses. More importantly, by suppressing these pathways, restoration of NOX2-derived ROS specifically in pDCs protected against lupus. These discoveries explain the causative effect of dysfunctional NCF1 in lupus and demonstrate the protective role of pDC-derived ROS in disease development driven by NCF1-dependent ROS deficiency.
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