Serine is an essential metabolite for effector T cell expansion
Open accessAbstract
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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- 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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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