Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species

Abstract The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMP...

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Autores principales:	Anouk Lepez, Tiphène Pirnay, Sébastien Denanglaire, David Perez-Morga, Marjorie Vermeersch, Oberdan Leo, Fabienne Andris
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c385a8aea9048439529ca4cda5d6ca6
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spelling	oai:doaj.org-article:9c385a8aea9048439529ca4cda5d6ca62021-12-02T16:18:02ZLong-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species10.1038/s41598-020-78715-22045-2322https://doaj.org/article/9c385a8aea9048439529ca4cda5d6ca62020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78715-2https://doaj.org/toc/2045-2322Abstract The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term proliferation but required for sustained long-term T cell proliferation and effector/memory T cell survival. In particular, AMPK promoted accumulation of effector/memory T cells in competitive homeostatic proliferation settings. Transplantation of AMPK-deficient hematopoïetic cells into allogeneic host recipients led to a reduced graft-versus-host disease, further bolstering a role for AMPK in the expansion and pathogenicity of effector T cells. Mechanistically, AMPK expression enhances the mitochondrial membrane potential of T cells, limits reactive oxygen species (ROS) production, and resolves ROS-mediated toxicity. Moreover, dampening ROS production alleviates the proliferative defect of AMPK-deficient T cells, therefore indicating a role for an AMPK-mediated ROS control of T cell fitness.Anouk LepezTiphène PirnaySébastien DenanglaireDavid Perez-MorgaMarjorie VermeerschOberdan LeoFabienne AndrisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anouk Lepez Tiphène Pirnay Sébastien Denanglaire David Perez-Morga Marjorie Vermeersch Oberdan Leo Fabienne Andris Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
description	Abstract The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term proliferation but required for sustained long-term T cell proliferation and effector/memory T cell survival. In particular, AMPK promoted accumulation of effector/memory T cells in competitive homeostatic proliferation settings. Transplantation of AMPK-deficient hematopoïetic cells into allogeneic host recipients led to a reduced graft-versus-host disease, further bolstering a role for AMPK in the expansion and pathogenicity of effector T cells. Mechanistically, AMPK expression enhances the mitochondrial membrane potential of T cells, limits reactive oxygen species (ROS) production, and resolves ROS-mediated toxicity. Moreover, dampening ROS production alleviates the proliferative defect of AMPK-deficient T cells, therefore indicating a role for an AMPK-mediated ROS control of T cell fitness.
format	article
author	Anouk Lepez Tiphène Pirnay Sébastien Denanglaire David Perez-Morga Marjorie Vermeersch Oberdan Leo Fabienne Andris
author_facet	Anouk Lepez Tiphène Pirnay Sébastien Denanglaire David Perez-Morga Marjorie Vermeersch Oberdan Leo Fabienne Andris
author_sort	Anouk Lepez
title	Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
title_short	Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
title_full	Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
title_fullStr	Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
title_full_unstemmed	Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species
title_sort	long-term t cell fitness and proliferation is driven by ampk-dependent regulation of reactive oxygen species
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9c385a8aea9048439529ca4cda5d6ca6
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Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species

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