T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes.

Détails

ID Serval
serval:BIB_4A3DFD95BCCC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes.
Périodique
Nature
Auteur(s)
Guarda G., Dostert C., Staehli F., Cabalzar K., Castillo R., Tardivel A., Schneider P., Tschopp J.
ISSN
1476-4687[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
460
Numéro
7252
Pages
269-273
Langue
anglais
Résumé
Inflammation is a protective attempt by the host to remove injurious stimuli and initiate the tissue healing process. The inflammatory response must be actively terminated, however, because failure to do so can result in 'bystander' damage to tissues and diseases such as arthritis or type-2 diabetes. Yet the mechanisms controlling excessive inflammatory responses are still poorly understood. Here we show that mouse effector and memory CD4(+) T cells abolish macrophage inflammasome-mediated caspase-1 activation and subsequent interleukin 1beta release in a cognate manner. Inflammasome inhibition is observed for all tested NLRP1 (commonly called NALP1) and NLRP3 (NALP3 or cryopyrin) activators, whereas NLRC4 (IPAF) inflammasome function and release of other inflammatory mediators such as CXCL2, interleukin 6 and tumour necrosis factor are not affected. Suppression of the NLRP3 inflammasome requires cell-to-cell contact and can be mimicked by macrophage stimulation with selected ligands of the tumour necrosis factor family, such as CD40L (also known as CD40LG). In a NLRP3-dependent peritonitis model, effector CD4(+) T cells are responsible for decreasing neutrophil recruitment in an antigen-dependent manner. Our findings reveal an unexpected mechanism of inflammasome inhibition, whereby effector and memory T cells suppress potentially damaging inflammation, yet leave the primary inflammatory response, crucial for the onset of immunity, intact.
Mots-clé
Adaptor Proteins, Signal Transducing/antagonists & inhibitors, Adaptor Proteins, Signal Transducing/metabolism, Animals, Antigens/immunology, Apoptosis Regulatory Proteins/antagonists & inhibitors, Apoptosis Regulatory Proteins/metabolism, Bone Marrow Cells/cytology, CD4-Positive T-Lymphocytes/immunology, Carrier Proteins/antagonists & inhibitors, Carrier Proteins/metabolism, Caspase 1/metabolism, Cells, Cultured, Immunity, Innate/immunology, Immunologic Memory, Inflammation/immunology, Inflammation/metabolism, Interleukin-1beta/immunology, Ligands, Macrophages/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neutrophils/immunology, Peritoneal Cavity/cytology, Tumor Necrosis Factors/immunology, Tumor Necrosis Factors/metabolism
Pubmed
Web of science
Création de la notice
11/11/2009 12:45
Dernière modification de la notice
20/08/2019 13:57
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