Multiple roles of caspase‐8 in cell death, inflammation, and innate immunity

Caspase‐8 is an apical caspase involved in the programmed form of cell death called apoptosis that is critically important for mammalian development and immunity. Apoptosis was historically described as immunologically silent in contrast to other types of programmed cell death such as necroptosis or...

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Published in:Journal of leukocyte biology Vol. 109; no. 1; pp. 121 - 141
Main Authors: Orning, Pontus, Lien, Egil
Format: Journal Article
Language:English
Published: United States Oxford University Press 01.01.2021
Subjects:
Animals
Apoptosis
caspase
Caspase 8 - immunology
Caspase-8
Cell death
Cell Death - immunology
Humans
Immune response
Immunity, Innate - immunology
Inflammasomes
Inflammation
Inflammation - immunology
Innate immunity
Kinases
Microorganisms
Mortality
Necroptosis
Pyroptosis
TNF
pyroptosis
apoptosis
inflammasomes
TNF
caspase
necroptosis
ISSN:0741-5400, 1938-3673, 1938-3673
Online Access:Get full text
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Summary:Caspase‐8 is an apical caspase involved in the programmed form of cell death called apoptosis that is critically important for mammalian development and immunity. Apoptosis was historically described as immunologically silent in contrast to other types of programmed cell death such as necroptosis or pyroptosis. Recent reports suggest considerable crosstalk between these different forms of cell death. It is becoming increasingly clear that caspase‐8 has many non‐apoptotic roles, participating in multiple processes including regulation of necroptosis (mediated by receptor‐interacting serine/threonine kinases, RIPK1‐RIPK3), inflammatory cytokine expression, inflammasome activation, and cleavage of IL‐1β and gasdermin D, and protection against shock and microbial infection. In this review, we discuss the involvement of caspase‐8 in cell death and inflammation and highlight its role in innate immune responses and in the relationship between different forms of cell death. Caspase‐8 is one of the central components in this type of crosstalk. Graphical Caspase‐8 is historically known as an initiator of extrinsic apoptosis, but has now been shown to regulate necroptosis, pyroptosis, inflammasome activation, and inflammation.
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Author contributions: Both authors contributed with literature search, writing and editing of the paper.
ISSN:0741-5400
1938-3673
1938-3673
DOI:10.1002/JLB.3MR0420-305R