Cited by 416Inflammasome and immune disordersContact Dermatitis and AllergiesImmune Response and Inflammation

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Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity

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Watanabe, Hideki, Gaide, Olivier, Pétrilli, Virginie, Martinon, Fabio, Contassot, Emmanuel, Roques, Stéphanie, Kummer, Jean A., Tschopp, Jürg, French, Lars E.·2007·Journal of Investigative Dermatology

DOI 10.1038/sj.jid.5700819

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Abstract

The inflammasome is a cytosolic protein complex regulating the activation of caspase-1, which cleaves the pro-inflammatory cytokines IL-1beta and IL-18 into their active form. The inflammasome is composed of a NACHT-, LRR- and pyrin (NALP) family member that acts as a sensor for danger signals and the adaptor protein apoptosis-associated speck-like protein containing a CARD domain (ASC), which allows the recruitment of caspase-1 in the complex. In the skin, exposure to contact sensitizers (CS) such as trinitro-chlorobenzene causes an immune response called contact hypersensitivity (CHS) or eczema. In this delayed-type hypersensitivity response, efficient priming of the adaptive immunity depends on the concomitant activation of the innate immune system, including IL-1beta/IL-18 activation in the skin. To determine if the inflammasome contributes to CHS, we have analyzed its capacity to react to CS in vitro and in vivo. We show here that key components of the inflammasome are present in human keratinocytes and that CS like trinitro-chlorobenzene induce caspase-1/ASC dependent IL-1beta and IL-18 processing and secretion. We also show that ASC- and NALP3-deficient mice display an impaired response to CS. These findings suggest that CS act as danger signals that activate the inflammasome in the skin, and reveal a new role of NALP3 and ASC as regulators of innate immunity in CHS.

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Authors: Watanabe, H., Gaide, O., Pétrilli, V., Martinon, F., Contassot, E., Roques, S., Kummer, J. A., Tschopp, J., & French, L. E.
Affiliations: University of Geneva (CH)
University of Lausanne (CH)
University Medical Center Utrecht (NL)
University Hospital Zurich (CH)
Corresponding author: Gaide, Olivier
French, Lars E.
ORCID: Watanabe, Hideki
Gaide, Olivier
Pétrilli, Virginie
Martinon, Fabio
Contassot, Emmanuel
Kummer, Jean A.
French, Lars E.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2007-08
Volume: 127
Issue: 8
Pages: 1956-1963
ISSN: 0022-202X (ISSN-L)
DOI: 10.1038/sj.jid.5700819
OpenAlex: W1963492948
Cited by: 416
References: 43
Citations by year: 2026: 7 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 12 · 2021: 13 · 2020: 19 · 2019: 22 · 2018: 15 · 2017: 21 · 2016: 30 · 2015: 19 · 2014: 35 · 2013: 28 · 2012: 36
FWCI: 12.71
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, 3045 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: National Science Foundation
Louis-Jeantet Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: inflammasome, NLRP3, ASC, caspase-1, IL-1β processing, contact hypersensitivity, contact sensitizers, keratinocytes, innate immunity, damage-associated molecular patterns
MeSH terms: NLR Family, Pyrin Domain-Containing 3 Protein, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Dermatitis, Contact, Dinitrofluorobenzene, Humans, Immunity, Innate, Inflammation, Picryl Chloride, Keratinocytes, Caspase 1, Interleukin-18, CARD Signaling Adaptor Proteins, Interleukin-1beta

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Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity

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