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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00115/full |
| _version_ | 1818933717036433408 |
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| author | Deborah Cluxton Andreea Petrasca Barry Moran Jean M. Fletcher Jean M. Fletcher |
| author_facet | Deborah Cluxton Andreea Petrasca Barry Moran Jean M. Fletcher Jean M. Fletcher |
| author_sort | Deborah Cluxton |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T04:52:49Z |
| format | Article |
| id | doaj.art-37c13f6c247347e2bb3bbf679083ed64 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T04:52:49Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-37c13f6c247347e2bb3bbf679083ed642022-12-21T19:52:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00115410044Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and GlycolysisDeborah Cluxton0Andreea Petrasca1Barry Moran2Jean M. Fletcher3Jean M. Fletcher4School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandSchool of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandIn 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00115/fullT cellsTh17 cellsTreg cellsimmunometabolismfatty acid synthesisglycolysis (glycolytic pathway) |
| spellingShingle | Deborah Cluxton Andreea Petrasca Barry Moran Jean M. Fletcher Jean M. Fletcher Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis Frontiers in Immunology T cells Th17 cells Treg cells immunometabolism fatty acid synthesis glycolysis (glycolytic pathway) |
| 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 | T cells Th17 cells Treg cells immunometabolism fatty acid synthesis glycolysis (glycolytic pathway) |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00115/full |
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