ArticleJournal of autoimmunity2017
Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye.
Article in Journal of autoimmunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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.
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Who cites it
59 citing papers in PubMed, 107 citations in OpenAlex.
- Okra eyelid patch versus sodium hyaluronate combined with ofloxacin eye drop in the treatment of meibomian gland dysfunction: a randomized controlled trial.BMC ophthalmology · 2026Trial
- Immune inflammatory targets and anti-inflammatory therapy in dry eye disease.International ophthalmology · 2026Review
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Mechanistic Insights Into UC-MSC Therapy in a BAC-Induced Dry Eye Model: TSG-6-Dependent Inhibition of the Th17/CCL20-CCR6 Chemotactic Axis.Investigative ophthalmology & visual science · 2026Article
- The Therapeutic Potential of Exosomes in Ocular Surface Diseases.Biomolecules · 2026Review
- Bifidobacterium breve BBr60 Enhances SCFA Levels and Restores NLRP3/NLRP6 Balance in the Gut to Improve Motor Deficits in PD Mice.Probiotics and antimicrobial proteins · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles for dry eye disease: principles, progress, and challenges.Extracellular vesicles and circulating nucleic acids · 2026Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Autophagy Impairment-Derived SQSTM1 Accumulation Promotes Ferroptosis in Corneal Epithelial Cells Through ACSL4 in Dry Eye.Investigative ophthalmology & visual science · 2025Article
- Destructive and protective effects and therapeutic targets of IL-36 family cytokines in dry eye disease.The ocular surface · 2025Article
- Caspase 3/GSDME-Mediated Corneal Epithelial Pyroptosis Promotes Dry Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Oxidative Stress in Dry Eye Disease: A Bibliometric Analysis.Clinical ophthalmology (Auckland, N.Z.) · 2025Review
- Bile acids in follicular fluid: potential new therapeutic targets and predictive markers for women with diminished ovarian reserve.Journal of ovarian research · 2024Article
- Multifaceted mitochondrial as a novel therapeutic target in dry eye: insights and interventions.Cell death discovery · 2024Review
- Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model.Investigative ophthalmology & visual science · 2024Article
- Ameliorative effects ofIntegrative medicine research · 2024Article
- Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage.Journal of nanobiotechnology · 2024Article
- Mitochondrial DNA-Activated cGAS-STING Signaling in Environmental Dry Eye.Investigative ophthalmology & visual science · 2024Article
- Differential Efficacy of Small Molecules Dynasore and Mdivi-1 for the Treatment of Dry Eye Epitheliopathy or as a Countermeasure for Nitrogen Mustard Exposure of the Ocular Surface.The Journal of pharmacology and experimental therapeutics · 2024Article
- KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.Investigative ophthalmology & visual science · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress. Activated NLRP3 with suppressed NLRP6 stimulates caspase-1 activation that leads to IL-1β and IL-18 maturation and secretion. NLRP3-independent caspase-8 noncanonically activates caspase-1 via reciprocal regulation of NLRP3/NLRP6-mediated inflammasomes. Reactive oxygen species-induced mitochondrial DNA oxidative damage and BRCC36 deubiquitinating activity provide a missing link and mechanism by which innate immunity responds to environmental stress via caspase-8-involved NLRP3/NLRP6 inflammasomes.
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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.