XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.
Détails
ID Serval
serval:BIB_BE672E83ECEB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.
Périodique
Cell reports
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
18/07/2017
Peer-reviewed
Oui
Volume
20
Numéro
3
Pages
668-682
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations.
Mots-clé
Animals, Caspase 8/genetics, Caspase 8/metabolism, Cell Death, Inhibitor of Apoptosis Proteins/deficiency, Inhibitor of Apoptosis Proteins/genetics, Inhibitor of Apoptosis Proteins/metabolism, Interleukin-1beta/genetics, Interleukin-1beta/metabolism, Mice, Mice, Knockout, Myeloid Differentiation Factor 88/genetics, Myeloid Differentiation Factor 88/metabolism, Proteolysis, Receptor-Interacting Protein Serine-Threonine Kinases/genetics, Receptor-Interacting Protein Serine-Threonine Kinases/metabolism, TNF Receptor-Associated Factor 2/genetics, TNF Receptor-Associated Factor 2/metabolism, Toll-Like Receptors/genetics, Toll-Like Receptors/metabolism, NLRP3, RIPK3, TNFR2, Toll-like receptor, XIAP, autoinflammatory disease, cIAP1, caspase-8, interferon, necroptosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/09/2018 21:01
Dernière modification de la notice
21/08/2019 6:35