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Critical Role for NALP3/CIAS1/Cryopyrin in Innate and Adaptive Immunity through Its Regulation of Caspase-1
Open accessAbstract
Mutations in the NALP3/CIAS1/cryopyrin gene are linked to three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and chronic infantile neurologic cutaneous and articular syndrome. NALP3, with the adaptor molecule ASC, has been proposed to form a caspase-1-activating "inflammasome," a complex with pro-IL1beta-processing activity. Here, we demonstrate the effect of NALP3 deficiency on caspase-1 function. NALP3 was essential for the ATP-driven activation of caspase-1 in lipopolysaccharide-stimulated macrophages and for the efficient secretion of the caspase-1-dependent cytokines IL-1alpha, IL-1beta, and IL-18. IL-1beta has been shown to play a key role in contact hypersensitivity; we show that ASC- and NALP3-deficient mice also demonstrate an impaired contact hypersensitivity response to the hapten trinitrophenylchloride. NALP3, however, was not required for caspase-1 activation by Salmonella typhimurium, and NALP3 deficiency only partially protects mice from the lethal effects of endotoxin. These data suggest that NALP3 plays a specific role in the caspase-1 activation pathway.
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“and contact hypersensitivity appears to be mediated by the inflammasome/IL-1β pathway (44,45).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [45]
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Metadata
- Authors
- Sutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., & Flavell, R. A.
- Affiliations
- Yale University (US)
- Jagiellonian University (PL)
- Takeda Oncology (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Flavell, Richard A.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 24
- Issue
- 3
- Pages
- 317-327
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2120815988
- Cited by
- 980
- References
- 42
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 35 · 2023: 35 · 2022: 31 · 2021: 31 · 2020: 46 · 2019: 50 · 2018: 25 · 2017: 41 · 2016: 42 · 2015: 43 · 2014: 65 · 2013: 57 · 2012: 74
- FWCI
- 30.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- 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, CIAS1, caspase-1, inflammasome, autoinflammatory disease, Muckle-Wells syndrome, familial cold autoinflammatory syndrome, ASC, IL-1β, IL-18, IL-1α, contact hypersensitivity, lipopolysaccharide, macrophages, endotoxin lethality, innate immunity, adaptive immunity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adenosine Triphosphate, Animals, Autoimmune Diseases, Carrier Proteins, Cytoskeletal Proteins, Enzyme Activation, Immunity, Innate, Interleukin-1, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, RNA, Messenger, Salmonella typhimurium, Shock, Septic, Caspase 1, Apoptosis Regulatory Proteins, Toll-Like Receptors, Mice, CARD Signaling Adaptor Proteins
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