The influence of DRAK2 on inducing T cell differentiation through metabolic reprogramming 9056

Abstract Description Metabolic reprogramming of T cells driven by activation marks a significant shift in reliance on metabolic processes and is a component in determining how T cells differentiate. In autoimmune diseases such as multiple sclerosis (MS) that involve the degradation of myelin by autoreactive T cells, differentiation of regulatory T cells is vital for their suppressive function. Previously, an experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to determine the importance of the death-associated protein kinase-related apoptosis-inducing protein kinase 2 (DRAK2), a regulator of T cell proliferation, and a novel resistance to EAE in the absence of DRAK2. In addition, the depletion of regulatory T cells in an EAE DRAK2-/- model restores EAE sensitivity. Here, we examine the role of DRAK2 and its influence on T cell metabolic reprogramming and differentiation. By manipulating cell metabolic processes of fatty acid β-oxidation (FAO) and autophagy then subsequently quantifying lipid droplet accumulation and mitochondrial membrane potential, we find that DRAK2 is a suppressor of autophagy and FAO, although it is unclear whether this is a downstream effect or independent process. These results reveal how DRAK2 influences metabolic signaling leading to differences in T cell differentiation, and suggests how DRAK2 can be used as a potential target in MS therapeutics through its capabilities to induce differentiation of regulatory or conventional T cells. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)