Regulation of inflammasome activation

<jats:title>Summary</jats:title><jats:p>Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto‐inflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen‐associated molecular patterns or danger‐associated molecular patterns by a nucleotide‐binding domain and leucine‐rich repeat receptor (<jats:styled-content style="fixed-case">NLR</jats:styled-content>) or absent in melanoma 2 (AIM2)‐like receptors (<jats:styled-content style="fixed-case">ALR</jats:styled-content>). <jats:styled-content style="fixed-case">NLR</jats:styled-content>s and <jats:styled-content style="fixed-case">ALR</jats:styled-content>s engage caspase‐1, in most cases requiring the adapter protein apoptosis‐associated speck‐like protein containing a <jats:styled-content style="fixed-case">CARD</jats:styled-content> (<jats:styled-content style="fixed-case">ASC</jats:styled-content>), to catalyze proteolytic cleavage of pro‐interleukin‐1β (pro‐<jats:styled-content style="fixed-case">IL</jats:styled-content>‐1β) and pro‐<jats:styled-content style="fixed-case">IL</jats:styled-content>‐18 and drive pyroptosis. Recent studies indicate that caspase‐8, caspase‐11, <jats:styled-content style="fixed-case">IL</jats:styled-content>‐1R–associated kinases (<jats:styled-content style="fixed-case">IRAK</jats:styled-content>), and receptor‐interacting protein (<jats:styled-content style="fixed-case">RIP</jats:styled-content>) kinases contribute to inflammasome functions. In addition, post‐translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in <jats:styled-content style="fixed-case">NLRP</jats:styled-content>1, <jats:styled-content style="fixed-case">NLRP</jats:styled-content>3, <jats:styled-content style="fixed-case">NLRC</jats:styled-content>4, and <jats:styled-content style="fixed-case">AIM</jats:styled-content>2 are linked with the development of auto‐inflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease.</jats:p>