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Serine Is an Essential Metabolite for Effector T Cell Expansion.

  • Ma EH Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Bantug G Department of Biomedicine, Immunobiology, University of Basel, 4031 Basel, Switzerland.
  • Griss T Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Condotta S Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada; Microbiome and Disease Tolerance Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Johnson RM Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
  • Samborska B Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Mainolfi N Raze Therapeutics, 400 Technology Square, 10th Floor, Cambridge, MA 02139, USA.
  • Suri V Raze Therapeutics, 400 Technology Square, 10th Floor, Cambridge, MA 02139, USA.
  • Guak H Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Balmer ML Department of Biomedicine, Immunobiology, University of Basel, 4031 Basel, Switzerland.
  • Verway MJ Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Raissi TC Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Tsui H Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Boukhaled G Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Henriques da Costa S MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Frezza C MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Krawczyk CM Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Friedman A Raze Therapeutics, 400 Technology Square, 10th Floor, Cambridge, MA 02139, USA.
  • Manfredi M Raze Therapeutics, 400 Technology Square, 10th Floor, Cambridge, MA 02139, USA.
  • Richer MJ Department of Microbiology and Immunology, McGill University, Montreal, QC H3G 1Y6, Canada; Microbiome and Disease Tolerance Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Hess C Department of Biomedicine, Immunobiology, University of Basel, 4031 Basel, Switzerland.
  • Jones RG Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: russell.jones@mcgill.ca.
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  • 2017-01-24
Published in:
  • Cell metabolism. - 2017
Phgdh
Shmt
T cell
glycolysis
immunometabolism
immunotherapy
metabolic reprogramming
metabolism
serine
serine biosynthesis
Animals
Carbon
Cell Cycle Checkpoints
Cell Proliferation
Diet
Energy Metabolism
Extracellular Space
Glycine
Listeria monocytogenes
Metabolic Networks and Pathways
Metabolome
Mice, Inbred C57BL
Purine Nucleotides
Serine
T-Lymphocytes
English During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/160020
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