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Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis

In this study we examined the metabolic requirements of human T helper cells and the effect of manipulating metabolic pathways in Th17 and Treg cells. The Th17:Treg cell axis is dysregulated in a number of autoimmune or inflammatory diseases and therefore it is of key importance to identify novel st...

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Autores principales: Cluxton, Deborah, Petrasca, Andreea, Moran, Barry, Fletcher, Jean M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369198/
https://www.ncbi.nlm.nih.gov/pubmed/30778354
http://dx.doi.org/10.3389/fimmu.2019.00115
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author Cluxton, Deborah
Petrasca, Andreea
Moran, Barry
Fletcher, Jean M.
author_facet Cluxton, Deborah
Petrasca, Andreea
Moran, Barry
Fletcher, Jean M.
author_sort Cluxton, Deborah
collection PubMed
description In this study we examined the metabolic requirements of human T helper cells and the effect of manipulating metabolic pathways in Th17 and Treg cells. The Th17:Treg cell axis is dysregulated in a number of autoimmune or inflammatory diseases and therefore it is of key importance to identify novel strategies to modulate this axis in favor of Treg cells. We investigated the role of carbohydrate and fatty acid metabolism in the regulation of human memory T helper cell subsets, in order to understand how T cells are regulated at the site of inflammation where essential nutrients including oxygen may be limiting. We found that Th17 lineage cells primarily utilize glycolysis, as glucose-deprivation and treatment with rapamycin resulted in a reduction in these cells. On the other hand, Treg cells exhibited increased glycolysis, mitochondrial respiration, and fatty acid oxidation, whereas Th17 cells demonstrated a reliance upon fatty acid synthesis. Treg cells were somewhat reliant on glycolysis, but to a lesser extent than Th17 cells. Here we expose a fundamental difference in the metabolic requirements of human Treg and Th17 cells and a possible mechanism for manipulating the Th17:Treg cell axis.
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spelling pubmed-63691982019-02-18 Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis Cluxton, Deborah Petrasca, Andreea Moran, Barry Fletcher, Jean M. Front Immunol Immunology In this study we examined the metabolic requirements of human T helper cells and the effect of manipulating metabolic pathways in Th17 and Treg cells. The Th17:Treg cell axis is dysregulated in a number of autoimmune or inflammatory diseases and therefore it is of key importance to identify novel strategies to modulate this axis in favor of Treg cells. We investigated the role of carbohydrate and fatty acid metabolism in the regulation of human memory T helper cell subsets, in order to understand how T cells are regulated at the site of inflammation where essential nutrients including oxygen may be limiting. We found that Th17 lineage cells primarily utilize glycolysis, as glucose-deprivation and treatment with rapamycin resulted in a reduction in these cells. On the other hand, Treg cells exhibited increased glycolysis, mitochondrial respiration, and fatty acid oxidation, whereas Th17 cells demonstrated a reliance upon fatty acid synthesis. Treg cells were somewhat reliant on glycolysis, but to a lesser extent than Th17 cells. Here we expose a fundamental difference in the metabolic requirements of human Treg and Th17 cells and a possible mechanism for manipulating the Th17:Treg cell axis. Frontiers Media S.A. 2019-02-04 /pmc/articles/PMC6369198/ /pubmed/30778354 http://dx.doi.org/10.3389/fimmu.2019.00115 Text en Copyright © 2019 Cluxton, Petrasca, Moran and Fletcher. 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
Cluxton, Deborah
Petrasca, Andreea
Moran, Barry
Fletcher, Jean M.
Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title_full Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title_fullStr Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title_full_unstemmed Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title_short Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis
title_sort differential regulation of human treg and th17 cells by fatty acid synthesis and glycolysis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369198/
https://www.ncbi.nlm.nih.gov/pubmed/30778354
http://dx.doi.org/10.3389/fimmu.2019.00115
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