Please use this identifier to cite or link to this item: https://doi.org/10.3389/fimmu.2019.00868
Title: Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
Authors: Zeng, Q
Mallilankaraman, K 
Schwarz, H 
Keywords: Akt
CD137L-DC
glycolysis
lipid synthesis
mTOR
metabolism
succinate
Issue Date: 1-Jan-2019
Citation: Zeng, Q, Mallilankaraman, K, Schwarz, H (2019-01-01). Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs. Frontiers in immunology 10 : 868-. ScholarBank@NUS Repository. https://doi.org/10.3389/fimmu.2019.00868
Abstract: CD137 ligand-induced dendritic cells (CD137L-DCs) are a new type of dendritic cells (DCs) that induce strong cytotoxic T cell responses. Investigating the metabolic activity as a potential contributing factor for their potency, we find a significantly higher rate of glycolysis in CD137L-DCs than in granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 induced monocyte-derived DCs (moDCs). Using unbiased screening, Akt-mTORC1 activity was found to be significantly higher throughout the differentiation and maturation of CD137L-DCs than that of moDCs. Furthermore, this higher activity of the Akt-mTORC1 pathway is responsible for the significantly higher glycolysis rate in CD137L-DCs than in moDCs. Inhibition of Akt during maturation or inhibition of glycolysis during and after maturation resulted in suppression of inflammatory DCs, with mature CD137L-DCs being the most affected ones. mTORC1, instead, was indispensable for the differentiation of both CD137L-DCs and moDCs. In contrast to its role in supporting lipid synthesis in murine bone marrow-derived DCs (BMDCs), the higher glycolysis rate in CD137L-DCs does not lead to a higher lipid content but rather to an accumulation of succinate and serine. These data demonstrate that the increased Akt-driven glycolysis underlies the higher activity of CD137L-DCs.
Source Title: Frontiers in immunology
URI: https://scholarbank.nus.edu.sg/handle/10635/155318
ISSN: 1664-3224
DOI: 10.3389/fimmu.2019.00868
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