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Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming

Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both...

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Autores principales: Simula, Luca, Pacella, Ilenia, Colamatteo, Alessandra, Procaccini, Claudio, Cancila, Valeria, Bordi, Matteo, Tregnago, Claudia, Corrado, Mauro, Pigazzi, Martina, Barnaba, Vincenzo, Tripodo, Claudio, Matarese, Giuseppe, Piconese, Silvia, Campello, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302735/
https://www.ncbi.nlm.nih.gov/pubmed/30540939
http://dx.doi.org/10.1016/j.celrep.2018.11.018
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author Simula, Luca
Pacella, Ilenia
Colamatteo, Alessandra
Procaccini, Claudio
Cancila, Valeria
Bordi, Matteo
Tregnago, Claudia
Corrado, Mauro
Pigazzi, Martina
Barnaba, Vincenzo
Tripodo, Claudio
Matarese, Giuseppe
Piconese, Silvia
Campello, Silvia
author_facet Simula, Luca
Pacella, Ilenia
Colamatteo, Alessandra
Procaccini, Claudio
Cancila, Valeria
Bordi, Matteo
Tregnago, Claudia
Corrado, Mauro
Pigazzi, Martina
Barnaba, Vincenzo
Tripodo, Claudio
Matarese, Giuseppe
Piconese, Silvia
Campello, Silvia
author_sort Simula, Luca
collection PubMed
description Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance.
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spelling pubmed-63027352018-12-27 Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming Simula, Luca Pacella, Ilenia Colamatteo, Alessandra Procaccini, Claudio Cancila, Valeria Bordi, Matteo Tregnago, Claudia Corrado, Mauro Pigazzi, Martina Barnaba, Vincenzo Tripodo, Claudio Matarese, Giuseppe Piconese, Silvia Campello, Silvia Cell Rep Article Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance. Cell Press 2018-12-11 /pmc/articles/PMC6302735/ /pubmed/30540939 http://dx.doi.org/10.1016/j.celrep.2018.11.018 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Simula, Luca
Pacella, Ilenia
Colamatteo, Alessandra
Procaccini, Claudio
Cancila, Valeria
Bordi, Matteo
Tregnago, Claudia
Corrado, Mauro
Pigazzi, Martina
Barnaba, Vincenzo
Tripodo, Claudio
Matarese, Giuseppe
Piconese, Silvia
Campello, Silvia
Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title_full Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title_fullStr Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title_full_unstemmed Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title_short Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
title_sort drp1 controls effective t cell immune-surveillance by regulating t cell migration, proliferation, and cmyc-dependent metabolic reprogramming
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302735/
https://www.ncbi.nlm.nih.gov/pubmed/30540939
http://dx.doi.org/10.1016/j.celrep.2018.11.018
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