ArticleThe EMBO journal2023
The lysosomal Ragulator complex activates NLRP3 inflammasome in vivo via HDAC6.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Potential mechanisms of natural products in improving gouty arthritis: Focusing on NLRP3 inflammasome regulation.Journal of pharmaceutical analysis · 2026Review
- Nrf2 promotes NLRP3 inflammasome assembly and activation by Klf9-TXNIP axis.Cell death discovery · 2026Article
- High-Throughput Screening Reveals That CeeNU Acts as a New NLRP3 Inflammasome Inhibitor.MedComm · 2026Article
- Identification of Histone Deacetylase Inhibitor Targeting Type I Interferon and B Cell Abnormalities in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Diverse Scaffolds Facilitate NLRP3 Clustering and Inflammasome Formation in Response to Perturbations in Cell Homeostasis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- The regulatory mechanism of NLRP3 inflammasome in the "immune paralytic-overactivation" imbalance in sepsis: the latest progress from molecular signaling to clinical translation.Frontiers in immunology · 2026Review
- Galectin-3 and the Glyco-Inflammatory Axis: A Missing Link to Residual Cardiovascular Risk in Coronary Artery Disease.Biomedicines · 2025Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Roles of Autophagy and Oxidative Stress in Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The Ragulator complex and lysosomal calcium release are crucial for cell migration.Life science alliance · 2025Article
- Straight A's: protein acylation in the S-activation and autophagic degradation of NOD-like receptors.Biochemical Society transactions · 2025Article
- Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Clustering of NLRP3 induced by membrane or protein scaffolds promotes inflammasome assembly.Nature communications · 2025Article
- Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions.Biomedicines · 2025Review
- Cross-Sectional Study Demonstrating Specificity of Iron Kinetics in Atrial Fibrillation.Circulation reports · 2025Article
- Review
- Revealing the dance of NLRP3: spatiotemporal patterns in inflammasome activation.Immunometabolism (Cobham, Surrey) · 2025Review
- The Progress of Immune Cells-induced Inflammatory Response in Gout.Current pharmaceutical design · 2025Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting in NLRP3 inflammasome activation. DL-all-rac-α-tocopherol, a synthetic form of vitamin E, inhibited the Lamtor1-HDAC6 interaction, resulting in diminished NLRP3 inflammasome activation. Further, DL-all-rac-α-tocopherol alleviated acute gouty arthritis and MSU-induced peritonitis. These results provide novel insights into the role of lysosomes in the activation of NLRP3 inflammasomes by the Ragulator complex.
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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 Socratic graph.