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Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity
Open accessAbstract
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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“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 [44]
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“For example, both murine and human keratinocytes express inflammasome components NLRP-3, ASC, caspase-1, IL-1β, and IL-18 (43,44).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [44]
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Metadata
- 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
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 127
- Issue
- 8
- Pages
- 1956-1963
- ISSN
- 0022-202X (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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