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2014 ; 35
(ä): 33-9
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Necroptotic signaling in adaptive and innate immunity
#MMPMID25042848
Lu JV
; Chen HC
; Walsh CM
Semin Cell Dev Biol
2014[Nov]; 35
(ä): 33-9
PMID25042848
show ga
The vertebrate immune system is highly dependent on cell death for efficient
responsiveness to microbial pathogens and oncogenically transformed cells. Cell
death pathways are vital to the function of many immune cell types during innate,
humoral and cellular immune responses. In addition, cell death regulation is
imperative for proper adaptive immune self-tolerance and homeostasis. While
apoptosis has been found to be involved in several of these roles in immunity,
recent data demonstrate that alternative cell death pathways are required. Here,
we describe the involvement of a programmed form of cellular necrosis called
"necroptosis" in immunity. We consider the signaling pathways that promote
necroptosis downstream of death receptors, type I transmembrane proteins of the
tumor necrosis factor (TNF) receptor family. The involvement of necroptotic
signaling through a "RIPoptosome" assembled in response to innate immune stimuli
or genotoxic stress is described. We also characterize the induction of
necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD
function. While necroptotic signaling remains poorly understood, it is clear that
this pathway is an essential component to effective vertebrate immunity.
|Adaptive Immunity/*immunology
[MESH]
|Caspase 8/immunology/metabolism
[MESH]
|Humans
[MESH]
|Immunity, Innate/*immunology
[MESH]
|Models, Immunological
[MESH]
|Necrosis/*immunology/metabolism
[MESH]
|Protein Kinases/immunology/metabolism
[MESH]
|Receptor-Interacting Protein Serine-Threonine Kinases/immunology/metabolism
[MESH]