Serine Is an Essential Metabolite for Effector T Cell Expansion

Cell Metab. 2017 Feb 7;25(2):345-357. doi: 10.1016/j.cmet.2016.12.011. Epub 2017 Jan 19.


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.

Keywords: Phgdh; Shmt; T cell; glycolysis; immunometabolism; immunotherapy; metabolic reprogramming; metabolism; serine; serine biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / metabolism
  • Cell Cycle Checkpoints
  • Cell Proliferation
  • Diet
  • Energy Metabolism
  • Extracellular Space / metabolism
  • Glycine
  • Listeria monocytogenes / immunology
  • Metabolic Networks and Pathways
  • Metabolome*
  • Mice, Inbred C57BL
  • Purine Nucleotides / biosynthesis
  • Serine / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*


  • Purine Nucleotides
  • Serine
  • Carbon
  • Glycine