Inhibition of succinate dehydrogenase activity impairs human T cell activation and function

Inhibition of succinate dehydrogenase activity impairs human T cell activation and function

Blog Article

Abstract T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the sheath functional and phenotypical differences between quiescent and activated T cells.Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation.However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation.

Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity.Similar effect of SDH inhibition were demonstrated in pre-activated T cell.Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect.

Taken together, our findings demonstrate that SDH enzyme fitness is Ball - Bag - Backpack critical for mounting and maintaining appropriate activation and function of human T cells.