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Serine Is an Essential Metabolite for Effector T Cell Expansion.

Ma, Eric H; Bantug, Glenn; Griss, Takla; Condotta, Stephanie; Johnson, Radia M; Samborska, Bozena; Mainolfi, Nello; Suri, Vipin; Guak, Hannah; Balmer, Maria L; Verway, Mark J; Raissi, Thomas C; Tsui, Harmony; Boukhaled, Giselle; Henriques da Costa, Sofia; Frezza, Christian; Krawczyk, Connie M; Friedman, Adam; Manfredi, Mark; Richer, Martin J; Hess, Christoph; Jones, Russell G.
Cell Metab; 25(2): 345-357, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28111214
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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