Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis
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2019Access:
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Cluxton D, Petrasca A, Moran B, Fletcher JM, Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis, Frontiers in Immunology, 10, 2019, 115-Download Item:
Abstract:
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.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
15/SPP/3212
Science Foundation Ireland (SFI)
12/RI/2340(7)
Author's Homepage:
http://people.tcd.ie/petrasanhttp://people.tcd.ie/fletchj
http://people.tcd.ie/moranba
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Frontiers in Immunology10
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Full text availableKeywords:
T cells, Th17 cells, Treg cells, Immunometabolism, Fatty acid synthesis, Glycolysis (glycolytic pathway), Immune modulation, Human T helper cellSubject (TCD):
Immunology, Inflammation & Infection , Glycolysis , HUMAN T-CELLS , LIPID METABOLISM , METABOLISM , Regulatory T cells , T CELLS , Th17 cellsDOI:
http://dx.doi.org/10.3389/fimmu.2019.001Metadata
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