Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity
| Autor: | Olivier Gaide, Jürg Tschopp, Stéphanie Roques, Emmanuel Contassot, Lars E. French, Virginie Pétrilli, Fabio Martinon, Jean Alain Kummer, Hideki Watanabe |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Interleukin-1beta NALP3 Picryl Chloride Dermatology Dermatitis Contact Pyrin domain Biochemistry AIM2 NLR Family Pyrin Domain-Containing 3 Protein medicine Humans NALP Molecular Biology Cells Cultured Inflammation Innate immune system biology Caspase 1 Interleukin-18 Inflammasome Cell Biology Acquired immune system Immunity Innate CARD Signaling Adaptor Proteins Cytoskeletal Proteins Immunology biology.protein CARD domain Dinitrofluorobenzene Carrier Proteins medicine.drug |
| Zdroj: | Journal of Investigative Dermatology. 127(8):1956-1963 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700819 |
| Popis: | The inflammasome is a cytosolic protein complex regulating the activation of caspase-1, which cleaves the pro-inflammatory cytokines IL-1 β 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-1 β /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-1 β 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. |
| Databáze: | OpenAIRE |
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