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Serine Is an Essential Metabolite for Effector T Cell Expansion
Ist Teil von
Cell metabolism, 2017-02, Vol.25 (2), p.345-357
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
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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•Enzymes of SGOC metabolism are upregulated upon T cell activation•Serine is required for optimal T cell proliferation in vitro and in vivo•Serine supports de novo purine biosynthesis in proliferating T cells•One-carbon units from formate can bypass serine starvation
Activated lymphocytes reprogram their metabolism to support rapid growth and proliferation. Ma et al. reveal an essential role for the non-essential amino acid serine in T cell-mediated immune responses and show that serine metabolism is required for optimal T cell proliferation by fueling one-carbon metabolism and nucleotide biosynthesis.