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The nucleic acid‐sensing inflammasomes
Author(s) -
Xiao Tsan Sam
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12281
Subject(s) - pyrin domain , inflammasome , biology , innate immune system , nucleic acid , microbiology and biotechnology , death domain , nalp3 , proinflammatory cytokine , aim2 , pattern recognition receptor , signal transduction , caspase 1 , receptor , biochemistry , immunology , programmed cell death , apoptosis , inflammation
Summary Inflammasomes are oligomeric signaling complexes that promote caspase activation and maturation of proinflammatory cytokines. Structural and biophysical studies have shed light on the mechanisms of nucleic acid recognition and signaling complex assembly involving the AIM 2 (absent in myeloma 2) and IFI 16 (γ‐interferon‐inducible protein 16) inflammasomes. However, our understanding of the mechanisms of the NLRP 3 (nucleotide‐binding oligomerization‐like receptor family, pyrin domain‐containing protein 3) activation, either by nucleic acids or by other reported stimuli, has remained elusive. Exciting recent progress on the filament formation by the ASC (apoptosis‐associated speck‐like protein containing a caspase recruitment domain) pyrin domain and the IFI 16–double stranded DNA complex has established that the formation of higher order polymers is one of the general mechanisms for signaling platform assembly in innate immune system. The paradigm‐changing discovery of the extracellular function of the NLRP 3– ASC inflammasome has opened the door for therapeutic targeting the inflammasome filament formation for various clinical conditions. Future characterization of the canonical and non‐canonical inflammasome complexes will undoubtedly reveal more surprises on their structure and function and enrich our understanding of the molecular mechanisms of ligand recognition, activation, and regulation.