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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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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. |
format | Online Article Text |
id | pubmed-3135356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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