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A Novel Role for Triglyceride Metabolism in Foxp3 Expression
Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the term...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701200/ https://www.ncbi.nlm.nih.gov/pubmed/31456800 http://dx.doi.org/10.3389/fimmu.2019.01860 |
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author | Howie, Duncan Ten Bokum, Annemieke Cobbold, Stephen Paul Yu, Zhanru Kessler, Benedikt M. Waldmann, Herman |
author_facet | Howie, Duncan Ten Bokum, Annemieke Cobbold, Stephen Paul Yu, Zhanru Kessler, Benedikt M. Waldmann, Herman |
author_sort | Howie, Duncan |
collection | PubMed |
description | Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the terminal step of triacylglycerol synthesis. In regulatory T-cells (Tregs), the conversion of diacylglycerols to triacylglycerols serves two additional purposes other than lipid storage. First, we demonstrate that it protects T cells from the toxic effects of saturated long chain fatty acids. Second, we show that Triglyceride formation is essential for limiting activation of protein kinase C via free diacyl glycerol moieties. Inhibition of DGAT1 resulted in elevated active PKC and nuclear NFKB, as well as impaired Foxp3 induction in response to TGFβ. Thus, Tregs utilize a positive feedback mechanism to promote sustained expression of Foxp3 associated with control of LD formation. |
format | Online Article Text |
id | pubmed-6701200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67012002019-08-27 A Novel Role for Triglyceride Metabolism in Foxp3 Expression Howie, Duncan Ten Bokum, Annemieke Cobbold, Stephen Paul Yu, Zhanru Kessler, Benedikt M. Waldmann, Herman Front Immunol Immunology Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the terminal step of triacylglycerol synthesis. In regulatory T-cells (Tregs), the conversion of diacylglycerols to triacylglycerols serves two additional purposes other than lipid storage. First, we demonstrate that it protects T cells from the toxic effects of saturated long chain fatty acids. Second, we show that Triglyceride formation is essential for limiting activation of protein kinase C via free diacyl glycerol moieties. Inhibition of DGAT1 resulted in elevated active PKC and nuclear NFKB, as well as impaired Foxp3 induction in response to TGFβ. Thus, Tregs utilize a positive feedback mechanism to promote sustained expression of Foxp3 associated with control of LD formation. Frontiers Media S.A. 2019-08-13 /pmc/articles/PMC6701200/ /pubmed/31456800 http://dx.doi.org/10.3389/fimmu.2019.01860 Text en Copyright © 2019 Howie, Ten Bokum, Cobbold, Yu, Kessler and Waldmann. 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 Howie, Duncan Ten Bokum, Annemieke Cobbold, Stephen Paul Yu, Zhanru Kessler, Benedikt M. Waldmann, Herman A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title | A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title_full | A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title_fullStr | A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title_full_unstemmed | A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title_short | A Novel Role for Triglyceride Metabolism in Foxp3 Expression |
title_sort | novel role for triglyceride metabolism in foxp3 expression |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701200/ https://www.ncbi.nlm.nih.gov/pubmed/31456800 http://dx.doi.org/10.3389/fimmu.2019.01860 |
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