Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2020

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

Résumé

Abstract 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.

Mots clés

Fichier principal
Vignette du fichier
s41598-020-78715-2.pdf (5.52 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04560830 , version 1 (30-04-2024)

Licence

Identifiants

Citer

Anouk Lepez, Tiphène Pirnay, Sébastien Denanglaire, David Perez-Morga, Marjorie Vermeersch, et al.. Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species. Scientific Reports, 2020, 10 (1), pp.21673. ⟨10.1038/s41598-020-78715-2⟩. ⟨hal-04560830⟩
4 Consultations
2 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More