NALP3 Forms an IL-1β-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder
Open accessAbstract
Mutations within the NALP3/cryopyrin/CIAS1 gene are responsible for three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. The NALP3 protein is homologous to NALP1, which is a component of the inflammasome, a molecular platform that activates the proinflammatory caspases-1 and -5. NALP3 (and other members of the NALP family) lacks the C-terminal, CARD-containing sequence of NALP1, and its role in caspase activation is unclear. Here, we report that NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity. Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders.
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The Nalp3 inflammasome has been linked to excessive IL-1β in autoinflammatory conditions like Muckle-Wells syndrome and in inflammatory diseases such as gout and pseudogout.
“The Nalp3 inflammasome is implicated in the pathological increase of IL-1β production in autoinflammatory syndromes, such as Muckle-Wells syndrome (22), as well as inflammatory processes, such as gout and pseudogout (7).”
From Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica (2008) · cites this paper as [22]
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- Authors
- Agostini, L., Martinon, F., Burns, K., McDermott, M. F., Hawkins, P. N., & Tschopp, J.
- Affiliations
- University of Lausanne (CH)
- Queen Mary University of London (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Tschopp, Jürg
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 20
- Issue
- 3
- Pages
- 319-325
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2134735862
- Cited by
- 1,768
- References
- 28
- Citations by year
- 2026: 44 · 2025: 70 · 2024: 66 · 2023: 73 · 2022: 97 · 2021: 74 · 2020: 90 · 2019: 90 · 2018: 61 · 2017: 84 · 2016: 70 · 2015: 101 · 2014: 102 · 2013: 106 · 2012: 88
- FWCI
- 24.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- NLRP3, Muckle-Wells syndrome, autoinflammatory disease, inflammasome, IL-1β processing, caspase-1, caspase-5, ASC, macrophages, familial cold autoinflammatory syndrome, CINCA, CARD domain, innate immunity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Autoimmune Diseases, Carrier Proteins, Cell Line, Cells, Cultured, Cytoskeletal Proteins, Humans, Inflammation, Interleukin-1, Macrophages, Mutation, Neoplasm Proteins, Protein Precursors, Protein Structure, Tertiary, Caspase 1, Macromolecular Substances, Adaptor Proteins, Signal Transducing, CARD Signaling Adaptor Proteins
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