Open AccessCaspase‐8: not so silently deadly
Author(s) -
Feltham Rebecca,
Vince James E,
Lawlor Kate E
Publication year - 2017
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1038/cti.2016.83
Subject(s) - pyroptosis , necroptosis , inflammasome , programmed cell death , microbiology and biotechnology , caspase 1 , nlrp1 , biology , ripk1 , caspase , crosstalk , innate immune system , apoptosis , caspase 8 , aim2 , inflammation , immunology , immune system , genetics , physics , optics
Apoptosis is a caspase‐dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3‐ and MLKL‐driven necroptosis, and caspase‐1/11‐dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase‐8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin‐1β (IL‐1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses. In view of these recent advances, human autoinflammatory diseases that are caused by mutations in cell death regulatory machinery are now associated with inappropriate inflammasome activation. In this review, we discuss the emerging crosstalk between cell death and innate immune cell inflammatory signalling, particularly focusing on novel non‐apoptotic functions of caspase‐8. We also highlight the growing number of autoinflammatory diseases that are associated with enhanced inflammasome function.