Glycogen metabolism supports effector function and energy homeostasis of dendritic cells

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.57-57.6
• Main Authors: Thwe, Phyu M., Beauchamp, Saritha, Amiel, Eyal
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.57.6

As professional antigen presenting cells of the immune system, dendritic cells (DCs) serve as a bridge between innate and adaptive immune responses. Activation of DCs by a stimulus through toll-like receptors (TLRs) is coupled with an increase in metabolic demand, which is fulfilled by a TLR-driven burst in glycolytic metabolism. Up-regulation of glycolysis in activated DCs provides metabolites and energy required for DC effector function, and inhibition of glycolysis impairs the survival and effector function of these cells. The prevailing model in the field proposes that TLR-driven glycolysis is sustained primarily by an increase in glucose uptake. While non-immune cells store glucose in the form of glycogen as an intracellular energy reserve, the role of glycogen metabolism in DCs has not been reported. Our data indicate that glycogen metabolism supports the activation of DCs, particularly before these cells increase the surface expression of glucose transporter-1 (GLUT1). We show that DCs express the enzymes essential for glycogen metabolism, that the glycogen metabolism is regulated upon TLR stimulation, and that inhibition of the glycogen metabolism in DCs impairs the expression of key maturation-associated molecules in these cells. Additionally, our data suggest that glycogen-derived glucose carbons feed into the tricarboxylic acid (TCA) cycle to support early maturation of DCs. These data indicate that the glycogen metabolism in DCs plays an important role in energy homeostasis in these cells to support their effector function. Understanding the role and regulatory mechanisms of glycogen metabolism in DCs has important implications for the future development of enhanced cellular based immunotherapy.