ArticleNature communications2023
Oxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 101 citations in OpenAlex.
- Targeted inhibition of inflammatory liver macrophages with a multifunctional nanoparticle ameliorates metabolic dysfunction-associated steatohepatitis.Bioactive materials · 2027Article
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Article
- Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- Mitochondria-Targeted Multimodal Nanotherapeutics Suppress Oxidized mtDNA-Driven Inflammation at the Source.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From disease model to therapeutic insight: An engineered hydrogel reveals the role of matrix viscous dissipation in intervertebral disc degeneration.Bioactive materials · 2026Article
- Mitochondria as convergence hubs for innate immunity pathways.Communications biology · 2026Review
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.Circulation research · 2026Review
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Biomimetic nanovesicles decorated with chemotactic and target membrane proteins for lupus nephritis treatment.Journal of nanobiotechnology · 2026Article
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Advances in the study of low-density neutrophils in rheumatic diseases.Frontiers in immunology · 2026Review
- Biological roles and clinical translation of low-density neutrophils in rheumatic, autoimmune and inflammatory diseases: paradigm reconstruction and unresolved questions.Frontiers in immunology · 2026Review
- Immunopathogenesis and Therapeutics of Systemic Lupus Erythematosus: an Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Gasdermins in neurodegeneration: emerging mechanisms and therapeutic targets.Cell death & disease · 2025Review
- GSDMD deficiency attenuates BPD by suppressing macrophage pyroptosis and promoting M2 polarization.Cell death discovery · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although extracellular DNA is known to form immune complexes (ICs) with autoantibodies in systemic lupus erythematosus (SLE), the mechanisms leading to the release of DNA from cells remain poorly characterized. Here, we show that the pore-forming protein, gasdermin D (GSDMD), is required for nuclear DNA and mitochondrial DNA (mtDNA) release from neutrophils and lytic cell death following ex vivo stimulation with serum from patients with SLE and IFN-γ. Mechanistically, the activation of FcγR downregulated Serpinb1 following ex vivo stimulation with serum from patients with SLE, leading to spontaneous activation of both caspase-1/caspase-11 and cleavage of GSDMD into GSDMD-N. Furthermore, mtDNA oxidization promoted GSDMD-N oligomerization and cell death. In addition, GSDMD, but not peptidyl arginine deiminase 4 is necessary for extracellular mtDNA release from low-density granulocytes from SLE patients or healthy human neutrophils following incubation with ICs. Using the pristane-induced lupus model, we show that disease severity is significantly reduced in mice with neutrophil-specific Gsdmd deficiency or following treatment with the GSDMD inhibitor, disulfiram. Altogether, our study highlights an important role for oxidized mtDNA in inducing GSDMD oligomerization and pore formation. These findings also suggest that GSDMD might represent a possible therapeutic target in SLE.
Indexed as
Identifiers
What OpenQuestion holds
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.