Serine Is an Essential Metabolite for Effector T Cell Expansion.
Ma, Eric H
Johnson, Radia M
Balmer, Maria L
Verway, Mark J
Raissi, Thomas C
Henriques da Costa, Sofia
Krawczyk, Connie M
Richer, Martin J
Jones, Russell G
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Ma, E. H., Bantug, G., Griss, T., Condotta, S., Johnson, R. M., Samborska, B., Mainolfi, N., et al. (2017). Serine Is an Essential Metabolite for Effector T Cell Expansion.. Cell metabolism, 25 (2), 482. https://doi.org/10.1016/j.cmet.2017.01.014
During immune challenge, T lymphocytes engage pathways of anabolic metabolism to meet the demands of clonal expansion and 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 T cell proliferation is highly dependent on extracellular serine, and that 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, we demonstrate that serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and that 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.
MRC (MC_UU_12022/1_do not transfer?)
External DOI: https://doi.org/10.1016/j.cmet.2017.01.014
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279462