Details

Autor(en) / Beteiligte

• 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.

Titel

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. [Display omitted] •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.