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Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of reactive oxygen species.
- Source :
-
Scientific reports [Sci Rep] 2020 Dec 10; Vol. 10 (1), pp. 21673. Date of Electronic Publication: 2020 Dec 10. - Publication Year :
- 2020
-
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.
- Subjects :
- AMP-Activated Protein Kinases genetics
AMP-Activated Protein Kinases physiology
Cell Survival genetics
Cells, Cultured
Gene Expression
Humans
Membrane Potential, Mitochondrial
Reactive Oxygen Species toxicity
Receptors, Antigen, T-Cell metabolism
Signal Transduction
AMP-Activated Protein Kinases metabolism
Cell Proliferation genetics
Reactive Oxygen Species metabolism
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33303820
- Full Text :
- https://doi.org/10.1038/s41598-020-78715-2