The metabolic drivers of IFN-γ release: glycolysis and acetyl CoA ride in the front seat.

Abstract

Interferon gamma (IFN-γ) is a pleotropic cytokine which is a central mediator of the immune response to pathogen infection, while also playing important roles in tumour suppression and the pathogenesis of various autoimmune diseases. Consequently, there is potential utility in the treatment of a number of pathological conditions via being able to modify IFN-γ secretion. T cells and natural killer (NK) cells are the primary IFN-γ sources, with metabolic rewiring prior to their activation and IFN-γ secretion in both a unifying feature. The mechanisms by which metabolic changes, particularly increased glycolysis, drive enhanced IFN-γ production are multi-faceted, but are likely focused on epigenetic changes via increased acetyl CoA levels which fuels histone acetylation. Herein, we discuss the mechanisms by which metabolic changes drive altered IFN-γ synthesis by immune cells.