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Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization

Watanabe, Hideki
Gehrke, Samuel
Tschopp, Jürg
Friedmann, Peter S.
French, Lars E.
Published in Journal of Immunology. 2008, vol. 180, no. 9, p. 5826-32
Abstract Efficient priming of adaptive immunity depends on danger signals provided by innate immune pathways. As an example, inflammasome-mediated activation of caspase-1 and IL-1beta is crucial for the development of reactive T cells targeting sensitizers like dinitrofluorobenzene (DNFB). Surprisingly, DNFB and dinitrothiocyanobenzene provide cross-reactive Ags yet drive opposing, sensitizing vs tolerizing, T cell responses. In this study, we show that, in mice, inflammasome-signaling levels can be modulated to turn dinitrothiocyanobenzene into a sensitizer and DNFB into a tolerizer, and that it correlates with the IL-6 and IL-12 secretion levels, affecting Th1, Th17, and regulatory T cell development. Hence, our data provide the first evidence that the inflammasome can define the type of adaptive immune response elicited by an Ag, and hint at new strategies to modulate T cell responses in vivo.
Keywords AnimalsAntigens/immunologyCaspase 1/immunologyCross Reactions/drug effects/immunologyDinitrobenzenes/pharmacologyDinitrofluorobenzene/pharmacologyHumansImmune Tolerance/drug effects/immunologyImmunity, Innate/drug effects/immunologyInflammation/immunologyInterleukin-1beta/immunologyInterleukin-2/immunologyInterleukin-6/immunologyMiceSignal Transduction/drug effects/immunologyT-Lymphocytes, Regulatory/immunologyTh1 Cells/immunology
PMID: 18424701
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Other version: http://www.jimmunol.org/cgi/content/full/180/9/5826
Research group Voies d'activation de l'immunité innée au niveau de la peau (156)
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WATANABE, Hideki et al. Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. In: Journal of Immunology, 2008, vol. 180, n° 9, p. 5826-32. https://archive-ouverte.unige.ch/unige:1063

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Deposited on : 2009-03-04

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