Phospho-enol pyruvate carboxykinase inhibition limits effector function in inflammatory T cells

Area of Science:

• Immunology
• Cellular Metabolism

Background:

• T cells shift from catabolic to anabolic metabolism upon activation.
• Regulators of anaplerosis and cataplerosis, like PEPCK, are crucial for T cell function.
• The role of PEPCK in T cell metabolism is not fully understood.

Purpose of the Study:

• To investigate the expression and function of PEPCK in T cells.
• To assess the impact of PEPCK inhibition on T cell activation and effector functions.

Main Methods:

• Assessed PEPCK expression in mouse T cells.
• Utilized pharmacological inhibitors to study PEPCK's role in T cell activation.

Main Results:

• Mitochondrial PEPCK (PEPCK-M) was upregulated post-T cell activation; cytosolic PEPCK-C was not detected.
• PEPCK inhibitors reduced CD8+ T cell cytotoxicity and CD4+/CD8+ T cell cytokine production.
• Inhibiting PEPCK decreased maximal mitochondrial respiration and suppressed T cell effector functions.

Conclusions:

• PEPCKs modulate mitochondrial metabolism to support T cell effector functions.
• Targeting PEPCK may offer a strategy to modulate T cell responses.