Serine Is an Essential Metabolite for Effector T Cell Expansion

Publication date: Available online 19 January 2017
Source:Cell Metabolism
Author(s): Eric H. Ma, Glenn Bantug, Takla Griss, Stephanie Condotta, Radia M. Johnson, Bozena Samborska, Nello Mainolfi, Vipin Suri, Hannah Guak, Maria L. Balmer, Mark J. Verway, Thomas C. Raissi, Harmony Tsui, Giselle Boukhaled, Sofia Henriques da Costa, Christian Frezza, Connie M. Krawczyk, Adam Friedman, Mark Manfredi, Martin J. Richer, Christoph Hess, Russell G. Jones
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.

Graphical abstract

Teaser

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.


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