Intracellular glycogen reserves fuel early glycolytic metabolism associated with dendritic cell maturation and immune function

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.202-202.31
• Main Authors: Amiel, Eyal, Thwe, Phyu M.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.202.31

Dendritic cells (DCs) serve as professional antigen presenting cells of the immune system. DCs activated by toll-like receptor (TLR) ligands undergo a process of maturation that is coupled with an increase in energy demand fulfilled by a TLR-driven burst in glycolytic metabolism. Up-regulation of glycolysis in activated DCs provides these cells with molecular building blocks and cellular energy required for DC effector function. Inhibition of glycolysis impairs both the survival and effector function of activated DCs. According to the prevailing model in the field, TLR-driven glycolysis in DCs is sustained primarily by increases in glucose uptake. We have characterized that DCs store glucose in the form of glycogen in the immature state and that glycogen functions as an intracellular energy reserve that is critical for early effector responses by these cells. Our data show that both human and mouse DCs express enzymes essential for glycogen metabolism and that glycogen synthesis is upregulated by inflammatory signals. In addition, we have observed that inhibition of glycogen metabolism significantly impairs key maturation parameters of these cells. Our findings indicate that glycogen metabolism in DCs plays an important role in supporting the effector function of these cells. This work uncovers a novel pathway for metabolic homeostasis in DCs and provides a new paradigm for how the metabolic requirements of DC activation are regulated.