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

Julianna Blagih, François Coulombe, Emma E Vincent, Fanny Dupuy, Gabriela Galicia-Vázquez, Ekaterina Yurchenko, Thomas C Raissi, Gerritje J W van der Windt, Benoit Viollet, Erika L Pearce, Jerry Pelletier, Ciriaco A Piccirillo, Connie M Krawczyk, Maziar Divangahi, Russell G Jones

Research output: Contribution to journalArticle (Academic Journal)peer-review

287 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41-54
Number of pages14
JournalImmunity
Volume42
Issue number1
DOIs
Publication statusPublished - 20 Jan 2015

Keywords

  • AMP-Activated Protein Kinases
  • Adaptation, Physiological
  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cells, Cultured
  • Cellular Reprogramming
  • Energy Metabolism
  • Glucose
  • Glutamine
  • Humans
  • Immunomodulation
  • Influenza A Virus, H1N1 Subtype
  • Lymphocyte Activation
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections
  • Protein Biosynthesis
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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