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Nat Rev Immunol ; 24(7): 518-535, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38374299

ABSTRACT

Inflammasomes are supramolecular complexes that form in the cytosol in response to pathogen-associated and damage-associated stimuli, as well as other danger signals that perturb cellular homoeostasis, resulting in host defence responses in the form of cytokine release and programmed cell death (pyroptosis). Inflammasome activity is closely associated with numerous human disorders, including rare genetic syndromes of autoinflammation, cardiovascular diseases, neurodegeneration and cancer. In recent years, a range of inflammasome components and their functions have been discovered, contributing to our knowledge of the overall machinery. Here, we review the latest advances in inflammasome biology from the perspective of structural and mechanistic studies. We focus on the most well-studied components of the canonical inflammasome - NAIP-NLRC4, NLRP3, NLRP1, CARD8 and caspase-1 - as well as caspase-4, caspase-5 and caspase-11 of the noncanonical inflammasome, and the inflammasome effectors GSDMD and NINJ1. These structural studies reveal important insights into how inflammasomes are assembled and regulated, and how they elicit the release of IL-1 family cytokines and induce membrane rupture in pyroptosis.


Subject(s)
Inflammasomes , Pyroptosis , Inflammasomes/immunology , Inflammasomes/metabolism , Humans , Pyroptosis/immunology , Animals , CARD Signaling Adaptor Proteins/metabolism , CARD Signaling Adaptor Proteins/immunology , CARD Signaling Adaptor Proteins/genetics , Neuronal Apoptosis-Inhibitory Protein/metabolism , Neuronal Apoptosis-Inhibitory Protein/immunology , Neuronal Apoptosis-Inhibitory Protein/genetics , Phosphate-Binding Proteins/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Caspases/metabolism , Caspases/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/immunology , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/immunology , NLR Proteins/metabolism , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/immunology , Gasdermins
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