Lecture series Infection & Immunity: "METABOLIC PROGRAMS CONTROLLING IMMUNE CELL FUNCTION" - Prof Tim Sparwasser

Recent advances in the field of immunometabolism support the notion that essential processes in T cell biology, such as TCR-mediated activation and T helper lineage differentiation, are closely linked to changes in the cellular metabolic programs. Although the main task of the intermediate metabolism is to provide the cell with a constant supply of energy and molecular precursors for the production of biomolecules, the dynamic regulation of metabolic pathways also plays an active role in shaping T cell responses. Key metabolic processes such as glycolysis, fatty acid and mitochondrial metabolism are now recognized as crucial players in T cell activation and differentiation, and their modulation can differentially affect the development of T helper cell lineages. We only begin to understand the diverse metabolic processes that T cells engage during their life cycle from naïve towards effector and memory T cells. Many milestone discoveries in this active area of research are based on the use of chemical inhibitors that have been shown to possess off-target effects, emphasizing the importance of genetic models to study immunometabolism. Following activation, T cells switch to fatty acid synthesis, demonstrating that de novo lipid synthesis actively supports T cell proliferation and differentiation. We could show previously that pharmacological or genetic ACC1 inhibition impairs T helper cell induction, with the strongest impact on Th17 development. Here we discuss the molecular mechanisms that link metabolic changes with the control of gene expression.

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