Caspase-8: Not so silently deadly

Rebecca Feltham, James E. Vince, Kate E. Lawlor

Research output: Contribution to journalReview ArticleResearchpeer-review

67 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere124
Number of pages13
JournalClinical & Translational Immunology
Volume6
Issue number1
DOIs
Publication statusPublished - 6 Jan 2017
Externally publishedYes

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