The NLRP3 inflammasome: activation and regulation.

Jie Xu, Gabriel Núñez

Journal: Trends in biochemical sciences 2023;48(4):331-344

PMID: 36336552

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Abstract

The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a cytoplasmic supramolecular complex that is activated in response to cellular perturbations triggered by infection and sterile injury. Assembly of the NLRP3 inflammasome leads to activation of caspase-1, which induces the maturation and release of interleukin-1β (IL-1β) and IL-18, as well as cleavage of gasdermin D (GSDMD), which promotes a lytic form of cell death. Production of IL-1β via NLRP3 can contribute to the pathogenesis of inflammatory disease, whereas aberrant IL-1β secretion through inherited NLRP3 mutations causes autoinflammatory disorders. In this review, we discuss recent developments in the structure of the NLRP3 inflammasome, and the cellular processes and signaling events controlling its assembly and activation.

Address: Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2022.10.002

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MeSH Terms: Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Signal Transduction, Caspase 1, Gene Expression, Interleukin-1beta