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Immunity. 2015 Jan 20;42(1):41-54. doi: 10.1016/j.immuni.2014.12.030. Epub 2015 Jan 2.

The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo.

Author information

1
Goodman Cancer Research Centre, McGill University, Montreal, QC, H3G 1Y6, Canada; Department of Physiology, McGill University, Montreal, QC, H3G 1Y6, Canada.
2
Departments of Medicine, Microbiology & Immunology, and Pathology, McGill International TB Centre, McGill University Health Centre and Research Institute, Meakins-Christie Laboratories, Montreal, QC, H2X 2P2, Canada.
3
Goodman Cancer Research Centre, McGill University, Montreal, QC, H3G 1Y6, Canada.
4
Goodman Cancer Research Centre, McGill University, Montreal, QC, H3G 1Y6, Canada; Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
5
Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada; McGill University Health Centre Research Institute, Montreal General Hospital, Montreal, QC, H3G 1A4, Canada.
6
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
7
Inserm, U1016, Institut Cochin, Sorbonne Paris Cité, Paris, France, 75014; CNRS, UMR 8104, Sorbonne Paris Cité, Paris, France, 75014; Université Paris Descartes, Sorbonne Paris Cité, Paris, France, 75014.
8
Goodman Cancer Research Centre, McGill University, Montreal, QC, H3G 1Y6, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada.
9
Goodman Cancer Research Centre, McGill University, Montreal, QC, H3G 1Y6, Canada; Department of Physiology, McGill University, Montreal, QC, H3G 1Y6, Canada. Electronic address: russell.jones@mcgill.ca.

Abstract

Naive T cells undergo metabolic reprogramming to support the increased energetic and biosynthetic demands of effector T cell function. However, how nutrient availability influences T cell metabolism and function remains poorly understood. Here we report plasticity in effector T cell metabolism in response to changing nutrient availability. Activated T cells were found to possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells lacking AMPKα1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKα1 is essential for T helper 1 (Th1) and Th17 cell development and primary T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity.

PMID:
25607458
DOI:
10.1016/j.immuni.2014.12.030
[Indexed for MEDLINE]
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