Title :

NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome

Author(s) :

Coombs, Jared [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Zamoshnikova, Alina [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Holley, Caroline [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Maddugoda, Madhavi [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Teo, Daniel Eng Thiam [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Chauvin, Camille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Poulin, Lionel [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Vitak, Nazarii [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Ross, Connie [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Mellacheruvu, Manasa [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Coll, Rebecca [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Heinz, Leonhard [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Burgener, Sabrina [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Emming, Stefan [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Chamaillard, Mathias [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Boucher, Dave [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]
Schroder, Kate [Auteur]
The University of Queensland [UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations]]

Journal title :

Science Signaling

Publisher :

American Association for the Advancement of Science (AAAS)

Publication date :

2024-01-23

ISSN :

1937-9145

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Inflammasomes are multiprotein complexes that drive inflammation and contribute to protective immunity against pathogens and immune pathology in autoinflammatory diseases. Inflammasomes assemble when an inflammasome scaffold ...
Show more >Inflammasomes are multiprotein complexes that drive inflammation and contribute to protective immunity against pathogens and immune pathology in autoinflammatory diseases. Inflammasomes assemble when an inflammasome scaffold protein senses an activating signal and forms a signaling platform with the inflammasome adaptor protein ASC. The NLRP subfamily of NOD-like receptors (NLRs) includes inflammasome nucleators (such as NLRP3) and also NLRP12, which is genetically linked to familial autoinflammatory disorders that resemble diseases caused by gain-of-function NLRP3 mutants that generate a hyperactive NLRP3 inflammasome. We performed a screen to identify ASC inflammasome–nucleating proteins among NLRs that have the canonical pyrin-NACHT-LRR domain structure. Only NLRP3 and NLRP6 could initiate ASC polymerization to form “specks,” and NLRP12 failed to nucleate ASC polymerization. However, wild-type NLRP12 inhibited ASC inflammasome assembly induced by wild-type and gain-of-function mutant NLRP3, an effect not seen with disease-associated NLRP12 mutants. The capacity of NLRP12 to suppress NLRP3 inflammasome assembly was limited to human NLRP3 and was not observed for wild-type murine NLRP3. Furthermore, peripheral blood mononuclear cells from patients with an NLRP12 mutant–associated inflammatory disorder produced increased amounts of the inflammatory cytokine IL-1β in response to NLRP3 stimulation. Thus, our findings provide insights into NLRP12 biology and suggest that NLRP3 inhibitors in clinical trials for NLRP3-driven diseases may also be effective in treating NLRP12-associated autoinflammatory diseases.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL