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TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis

Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) mRNA level and a higher le...

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Autores principales: Baijer, Jan, Déchamps, Nathalie, Perdry, Hervé, Morales, Pablo, Kerns, Sarah, Vasilescu, Alexandre, Baulande, Sylvain, Azria, David, Roméo, Paul Henri, Schmitz, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008295/
https://www.ncbi.nlm.nih.gov/pubmed/26982083
http://dx.doi.org/10.18632/oncotarget.7893
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author Baijer, Jan
Déchamps, Nathalie
Perdry, Hervé
Morales, Pablo
Kerns, Sarah
Vasilescu, Alexandre
Baulande, Sylvain
Azria, David
Roméo, Paul Henri
Schmitz, Annette
author_facet Baijer, Jan
Déchamps, Nathalie
Perdry, Hervé
Morales, Pablo
Kerns, Sarah
Vasilescu, Alexandre
Baulande, Sylvain
Azria, David
Roméo, Paul Henri
Schmitz, Annette
author_sort Baijer, Jan
collection PubMed
description Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity.
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spelling pubmed-50082952016-09-12 TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis Baijer, Jan Déchamps, Nathalie Perdry, Hervé Morales, Pablo Kerns, Sarah Vasilescu, Alexandre Baulande, Sylvain Azria, David Roméo, Paul Henri Schmitz, Annette Oncotarget Research Paper Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity. Impact Journals LLC 2016-03-16 /pmc/articles/PMC5008295/ /pubmed/26982083 http://dx.doi.org/10.18632/oncotarget.7893 Text en Copyright: © 2016 Baijer et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Baijer, Jan
Déchamps, Nathalie
Perdry, Hervé
Morales, Pablo
Kerns, Sarah
Vasilescu, Alexandre
Baulande, Sylvain
Azria, David
Roméo, Paul Henri
Schmitz, Annette
TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title_full TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title_fullStr TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title_full_unstemmed TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title_short TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
title_sort tnfsf10/trail regulates human t4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008295/
https://www.ncbi.nlm.nih.gov/pubmed/26982083
http://dx.doi.org/10.18632/oncotarget.7893
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