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Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs

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...

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Autores principales: Zeng, Qun, Mallilankaraman, Karthik, Schwarz, Herbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491642/
https://www.ncbi.nlm.nih.gov/pubmed/31068941
http://dx.doi.org/10.3389/fimmu.2019.00868
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author Zeng, Qun
Mallilankaraman, Karthik
Schwarz, Herbert
author_facet Zeng, Qun
Mallilankaraman, Karthik
Schwarz, Herbert
author_sort Zeng, Qun
collection PubMed
description 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.
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spelling pubmed-64916422019-05-08 Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs Zeng, Qun Mallilankaraman, Karthik Schwarz, Herbert Front Immunol Immunology 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. Frontiers Media S.A. 2019-04-24 /pmc/articles/PMC6491642/ /pubmed/31068941 http://dx.doi.org/10.3389/fimmu.2019.00868 Text en Copyright © 2019 Zeng, Mallilankaraman and Schwarz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zeng, Qun
Mallilankaraman, Karthik
Schwarz, Herbert
Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title_full Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title_fullStr Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title_full_unstemmed Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title_short Increased Akt-Driven Glycolysis Is the Basis for the Higher Potency of CD137L-DCs
title_sort increased akt-driven glycolysis is the basis for the higher potency of cd137l-dcs
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491642/
https://www.ncbi.nlm.nih.gov/pubmed/31068941
http://dx.doi.org/10.3389/fimmu.2019.00868
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