ArticleeLife2020
LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- A Review on Structural Insights into NLRP3 and NEK7: Domain Architecture, Subcellular Localization, and Their Interaction in Inflammasome Assembly and Signaling.Molecular neurobiology · 2026Review
- Spatial control of NLRP3 inflammasome assembly by membrane lipid composition.Communications biology · 2026Review
- Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling.The Journal of cell biology · 2026Article
- LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation.Genes & diseases · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Mechanism of action of two potent LRRC8/VRAC channel inhibitors.Research square · 2026Article
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- Activation of osmo-sensitive LRRC8 anion channels in macrophages is important for micro-crystallin joint inflammation.Nature communications · 2024Article
- Tunable Cytosolic Chloride Indicators for Real-Time Chloride Imaging in Live Cells.bioRxiv : the preprint server for biology · 2024Article
- Interactomic exploration of LRRC8A in volume-regulated anion channels.Cell death discovery · 2024Article
- Inflammasomes as regulators of mechano-immunity.EMBO reports · 2024Review
- Comprehensive review on the novel immunotherapy target: Leucine-rich repeat-containing 8A/volume-regulated anion channel.International journal of biological sciences · 2024Review
- Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function.Nature communications · 2023Article
- Targeting NLRP3 inflammasome for neurodegenerative disorders.Molecular psychiatry · 2023Review
- The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases.Molecular and cellular biochemistry · 2023Review
- Discovery of an inhibitor of DNA-driven inflammation that preferentially targets the AIM2 inflammasome.iScience · 2023Article
- ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain.Science advances · 2023Article
- cGAMP the travelling messenger.Frontiers in immunology · 2023Review
- Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022.Frontiers in pharmacology · 2023Article
- A detailed molecular network map and model of the NLRP3 inflammasome.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The NLRP3 inflammasome is a multi-molecular protein complex that converts inactive cytokine precursors into active forms of IL-1β and IL-18. The NLRP3 inflammasome is frequently associated with the damaging inflammation of non-communicable disease states and is considered an attractive therapeutic target. However, there is much regarding the mechanism of NLRP3 activation that remains unknown. Chloride efflux is suggested as an important step in NLRP3 activation, but which chloride channels are involved is still unknown. We used chemical, biochemical, and genetic approaches to establish the importance of chloride channels in the regulation of NLRP3 in murine macrophages. Specifically, we identify LRRC8A, an essential component of volume-regulated anion channels (VRAC), as a vital regulator of hypotonicity-induced, but not DAMP-induced, NLRP3 inflammasome activation. Although LRRC8A was dispensable for canonical DAMP-dependent NLRP3 activation, this was still sensitive to chloride channel inhibitors, suggesting there are additional and specific chloride sensing and regulating mechanisms controlling NLRP3.
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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.