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Mechanisms of necroptosis in T cells

Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8–deficient T cells, necroptosis occurs as the result of anti...

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Autores principales: Ch’en, Irene L., Tsau, Jennifer S., Molkentin, Jeffery D., Komatsu, Masaaki, Hedrick, Stephen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135356/
https://www.ncbi.nlm.nih.gov/pubmed/21402742
http://dx.doi.org/10.1084/jem.20110251
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author Ch’en, Irene L.
Tsau, Jennifer S.
Molkentin, Jeffery D.
Komatsu, Masaaki
Hedrick, Stephen M.
author_facet Ch’en, Irene L.
Tsau, Jennifer S.
Molkentin, Jeffery D.
Komatsu, Masaaki
Hedrick, Stephen M.
author_sort Ch’en, Irene L.
collection PubMed
description Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8–deficient T cells, necroptosis occurs as the result of antigen receptor–mediated activation. Here, through a genetic analysis, we show that necroptosis in caspase 8–deficient T cells is related neither to the programmed necrosis as defined by the requirement for mitochondrial cyclophilin D nor to autophagy as defined by the requirement for autophagy-related protein 7. Rather, survival of caspase 8–defective T cells can be completely rescued by loss of receptor-interacting serine-threonine kinase (Ripk) 3. Additionally, complementation of a T cell–specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice. In conjunction with previous work, we conclude that necroptosis in antigen-stimulated caspase 8–deficient T cells is the result of a novel Ripk1- and Ripk3-mediated pathway of cell death.
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spelling pubmed-31353562011-10-11 Mechanisms of necroptosis in T cells Ch’en, Irene L. Tsau, Jennifer S. Molkentin, Jeffery D. Komatsu, Masaaki Hedrick, Stephen M. J Exp Med Brief Definitive Report Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8–deficient T cells, necroptosis occurs as the result of antigen receptor–mediated activation. Here, through a genetic analysis, we show that necroptosis in caspase 8–deficient T cells is related neither to the programmed necrosis as defined by the requirement for mitochondrial cyclophilin D nor to autophagy as defined by the requirement for autophagy-related protein 7. Rather, survival of caspase 8–defective T cells can be completely rescued by loss of receptor-interacting serine-threonine kinase (Ripk) 3. Additionally, complementation of a T cell–specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice. In conjunction with previous work, we conclude that necroptosis in antigen-stimulated caspase 8–deficient T cells is the result of a novel Ripk1- and Ripk3-mediated pathway of cell death. The Rockefeller University Press 2011-04-11 /pmc/articles/PMC3135356/ /pubmed/21402742 http://dx.doi.org/10.1084/jem.20110251 Text en © 2011 Ch’en et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Ch’en, Irene L.
Tsau, Jennifer S.
Molkentin, Jeffery D.
Komatsu, Masaaki
Hedrick, Stephen M.
Mechanisms of necroptosis in T cells
title Mechanisms of necroptosis in T cells
title_full Mechanisms of necroptosis in T cells
title_fullStr Mechanisms of necroptosis in T cells
title_full_unstemmed Mechanisms of necroptosis in T cells
title_short Mechanisms of necroptosis in T cells
title_sort mechanisms of necroptosis in t cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135356/
https://www.ncbi.nlm.nih.gov/pubmed/21402742
http://dx.doi.org/10.1084/jem.20110251
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