Cited by 980Inflammasome and immune disordersImmune Response and InflammationAutoimmune and Inflammatory Disorders Research

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Critical Role for NALP3/CIAS1/Cryopyrin in Innate and Adaptive Immunity through Its Regulation of Caspase-1

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Sutterwala, Fayyaz S., Ogura, Yasunori, Szczepanik, Marian, Lara-Tejero, Maria, Lichtenberger, G. Scott, Grant, Ethan P., Bertin, John, Coyle, Anthony J., Galán, Jorge E., Askenase, Philip W., Flavell, Richard A.·2006·Immunity

DOI 10.1016/j.immuni.2006.02.004

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Abstract

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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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: Sutterwala, Fayyaz S.
Szczepanik, Marian
Bertin, John
Coyle, Anthony J.
Galán, Jorge E.
Askenase, Philip W.
Flavell, Richard A.
Venue: Immunity
Publisher: Elsevier BV
Published: 2006-03
Volume: 24
Issue: 3
Pages: 317-327
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2006.02.004
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2695 d)
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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Critical Role for NALP3/CIAS1/Cryopyrin in Innate and Adaptive Immunity through Its Regulation of Caspase-1

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