ArticleThe Journal of experimental medicine2016
Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
317 citing papers in PubMed, 2 syntheses or guidelines pooled it, 476 citations in OpenAlex.
- Diverse Roles of NETosis in the Pathogenesis of Lupus.Frontiers in immunology · 2022Pooled it
- Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations.Mitochondrion · 2021Pooled it
- Nucleic acid sensing pathways in kidney disease development.Nature reviews. Nephrology · 2026Review
- Considering evolved heat tolerance helps predict the immunological consequences of climate change.Seminars in immunopathology · 2026Review
- From mitochondria to innate immunity: The mtDNA-driven cGAS/STING-NLRP3 cascade and its therapeutic implications in neurodegenerative diseases (Review).Experimental and therapeutic medicine · 2026Review
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Mitochondrial Metabolic Reprogramming and Skin Immune Homeostasis: From Basic Mechanisms to Therapeutic Perspectives.Immune network · 2026Review
- Ginsenoside Compound K Mitigates Mitochondrial Fission Through Bile Acid Receptors/YAP Signaling to Counteract Podocyte Injury in Lupus Nephritis.Phytotherapy research : PTR · 2026Article
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- Review
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Systemic lupus pregnancies are characterized by an intrinsic pro-inflammatory monocyte transcriptome, driven by an aberrant miRNA signature.Journal of translational autoimmunity · 2026Article
- Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.Circulation research · 2026Review
- Mitophagy and Immune Infiltration in Primary Sjögren's Disease: Insights from Bioinformatics Analysis.International journal of molecular sciences · 2026Article
- Advances in nanotechnology for the diagnosis and management of autoimmune diseases.Asian journal of pharmaceutical sciences · 2026Review
- Antimitochondrial antibodies in systemic lupus erythematosus are associated with and predict nephritis, arterial vascular events, and mortality.Annals of the rheumatic diseases · 2026Article
- Advances in Elucidating the Mitochondrial DNA Mechanisms Underlying Ozone-Induced Inflammation.Toxics · 2026Review
- Targeting ST18-mediated pathomechanism in pemphigus vulgaris through voltage-dependent anion channel inhibition.Skin health and disease · 2026Article
- Proceedings of the 2Mediterranean journal of rheumatology · 2026Article
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
257 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byA CD42019
Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Autoantibodies against nucleic acids and excessive type I interferon (IFN) are hallmarks of human systemic lupus erythematosus (SLE). We previously reported that SLE neutrophils exposed to TLR7 agonist autoantibodies release interferogenic DNA, which we now demonstrate to be of mitochondrial origin. We further show that healthy human neutrophils do not complete mitophagy upon induction of mitochondrial damage. Rather, they extrude mitochondrial components, including DNA (mtDNA), devoid of oxidized (Ox) residues. When mtDNA undergoes oxidation, it is directly routed to lysosomes for degradation. This rerouting requires dissociation from the transcription factor A mitochondria (TFAM), a dual high-mobility group (HMG) protein involved in maintenance and compaction of the mitochondrial genome into nucleoids. Exposure of SLE neutrophils, or healthy IFN-primed neutrophils, to antiribonucleotide protein autoantibodies blocks TFAM phosphorylation, a necessary step for nucleoid dissociation. Consequently, Ox nucleoids accumulate within mitochondria and are eventually extruded as potent interferogenic complexes. In support of the in vivo relevance of this phenomenon, mitochondrial retention of Ox nucleoids is a feature of SLE blood neutrophils, and autoantibodies against Ox mtDNA are present in a fraction of patients. This pathway represents a novel therapeutic target in human SLE.
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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.