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Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate

Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with...

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Autores principales: Muroski, Megan E., Miska, Jason, Chang, Alan L., Zhang, Peng, Rashidi, Aida, Moore, Haley, Lopez-Rosas, Aurora, Han, Yu, Lesniak, Maciej S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517517/
https://www.ncbi.nlm.nih.gov/pubmed/28724939
http://dx.doi.org/10.1038/s41598-017-05556-x
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author Muroski, Megan E.
Miska, Jason
Chang, Alan L.
Zhang, Peng
Rashidi, Aida
Moore, Haley
Lopez-Rosas, Aurora
Han, Yu
Lesniak, Maciej S.
author_facet Muroski, Megan E.
Miska, Jason
Chang, Alan L.
Zhang, Peng
Rashidi, Aida
Moore, Haley
Lopez-Rosas, Aurora
Han, Yu
Lesniak, Maciej S.
author_sort Muroski, Megan E.
collection PubMed
description Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo.
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spelling pubmed-55175172017-07-20 Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate Muroski, Megan E. Miska, Jason Chang, Alan L. Zhang, Peng Rashidi, Aida Moore, Haley Lopez-Rosas, Aurora Han, Yu Lesniak, Maciej S. Sci Rep Article Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo. Nature Publishing Group UK 2017-07-19 /pmc/articles/PMC5517517/ /pubmed/28724939 http://dx.doi.org/10.1038/s41598-017-05556-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Muroski, Megan E.
Miska, Jason
Chang, Alan L.
Zhang, Peng
Rashidi, Aida
Moore, Haley
Lopez-Rosas, Aurora
Han, Yu
Lesniak, Maciej S.
Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title_full Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title_fullStr Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title_full_unstemmed Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title_short Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate
title_sort fatty acid uptake in t cell subsets using a quantum dot fatty acid conjugate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517517/
https://www.ncbi.nlm.nih.gov/pubmed/28724939
http://dx.doi.org/10.1038/s41598-017-05556-x
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