Serine Is an Essential Metabolite for Effector T Cell Expansion

Area of Science:

• Immunology
• Metabolic pathways
• Cellular metabolism

Background:

• T lymphocytes require anabolic metabolism for clonal expansion and effector functions during immune challenges.
• The serine, glycine, one-carbon (SGOC) metabolic network is upregulated by activated T cells.

Purpose of the Study:

• To investigate the critical role of the non-essential amino acid serine in effector T cell responses.
• To determine if extracellular serine is essential for T cell proliferation and function.

Main Methods:

• Analysis of serine, glycine, one-carbon (SGOC) metabolic network enzymes in activated T cells.
• Assessment of T cell expansion and function under varying extracellular serine concentrations.
• In vivo studies involving dietary serine restriction during pathogen challenge.

Main Results:

• Activated T cells rapidly increase serine processing into one-carbon metabolism.
• Extracellular serine is required for optimal T cell expansion, independent of glucose availability.
• Dietary serine restriction in vivo impairs pathogen-driven T cell expansion without affecting immune homeostasis.
• Serine provides glycine and one-carbon units for nucleotide biosynthesis in proliferating T cells.

Conclusions:

• Serine is a critical immunometabolite that directly modulates adaptive immunity.
• Serine availability controls T cell proliferative capacity, essential for effective immune responses.