Cited by 657T-cell and B-cell ImmunologyAmino Acid Enzymes and MetabolismCancer, Hypoxia, and Metabolism

Serine is an essential metabolite for effector T cell expansion

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Ma, Eric H., Bantug, Glenn, Griss, Takla, Condotta, Stephanie, Johnson, Radia M., Samborska, Bozena, Mainolfi, Nello, Suri, Vipin +14 more·2017·Cell Metabolism

Abstract

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.

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Crossref · 10.1016/j.cmet.2016.12.011

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Authors
Ma, E. H., Bantug, G., Griss, T., Condotta, S., Johnson, R. M., Samborska, B., Mainolfi, N., Suri, V., Guak, H., Balmer, M. L., Verway, M. J., Raissi, T. C., Tsui, H., Boukhaled, G., Henriques da Costa, S., Frezza, C., Krawczyk, C. M., Friedman, A., Manfredi, M., Richer, M. J., Hess, C., & Jones, R. G.
Affiliations
  • McGill University (CA)
  • University of Basel (CH)
  • University of Cambridge (GB)
Corresponding author
Jones, Russell G.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2017-02
Volume
25
Issue
2
Pages
345-357
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2579054962
Cited by
657
References
36
Citations by year
2026: 56 · 2025: 87 · 2024: 84 · 2023: 70 · 2022: 88 · 2021: 89 · 2020: 67 · 2019: 54 · 2018: 38 · 2017: 24
FWCI
22.61
Type
journal article
Language
en
Update notices
erratum (2017-02-07)
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fonds de Recherche du Québec - Santé
  • Canada Foundation for Innovation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030-153059, MOP-142259, TFRI-239585)
  • Terry Fox Research Institute
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
serine, effector T cell expansion, immunometabolism, T cell proliferation, formate, T cell activation, glucose metabolism
MeSH terms
Animals, Carbon, Diet, Energy Metabolism, Extracellular Space, Glycine, Listeria monocytogenes, Mice, Inbred C57BL, Purine Nucleotides, Serine, T-Lymphocytes, Cell Proliferation, Metabolic Networks and Pathways, Metabolome, Cell Cycle Checkpoints

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