Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/143717 |
| _version_ | 1811078757278023680 |
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| author | Lopes, Noella McIntyre, Claire Martin, Stefania Raverdeau, Mathilde Sumaria, Nital Kohlgruber, Ayano C Fiala, Gina J Agudelo, Leandro Z Dyck, Lydia Kane, Harry Douglas, Aaron Cunningham, Stephen Prendeville, Hannah Loftus, Roisin Carmody, Colleen Pierre, Philippe Kellis, Manolis Brenner, Michael Argüello, Rafael J Silva-Santos, Bruno Pennington, Daniel J Lynch, Lydia |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Lopes, Noella McIntyre, Claire Martin, Stefania Raverdeau, Mathilde Sumaria, Nital Kohlgruber, Ayano C Fiala, Gina J Agudelo, Leandro Z Dyck, Lydia Kane, Harry Douglas, Aaron Cunningham, Stephen Prendeville, Hannah Loftus, Roisin Carmody, Colleen Pierre, Philippe Kellis, Manolis Brenner, Michael Argüello, Rafael J Silva-Santos, Bruno Pennington, Daniel J Lynch, Lydia |
| author_sort | Lopes, Noella |
| collection | MIT |
| description | © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy. |
| first_indexed | 2024-09-23T11:05:03Z |
| format | Article |
| id | mit-1721.1/143717 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:05:03Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1437172023-12-07T14:41:44Z Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments Lopes, Noella McIntyre, Claire Martin, Stefania Raverdeau, Mathilde Sumaria, Nital Kohlgruber, Ayano C Fiala, Gina J Agudelo, Leandro Z Dyck, Lydia Kane, Harry Douglas, Aaron Cunningham, Stephen Prendeville, Hannah Loftus, Roisin Carmody, Colleen Pierre, Philippe Kellis, Manolis Brenner, Michael Argüello, Rafael J Silva-Santos, Bruno Pennington, Daniel J Lynch, Lydia Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy. 2022-07-13T16:46:20Z 2022-07-13T16:46:20Z 2021 2022-07-13T16:43:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/143717 Lopes, Noella, McIntyre, Claire, Martin, Stefania, Raverdeau, Mathilde, Sumaria, Nital et al. 2021. "Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments." Nature Immunology, 22 (2). en 10.1038/S41590-020-00848-3 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Lopes, Noella McIntyre, Claire Martin, Stefania Raverdeau, Mathilde Sumaria, Nital Kohlgruber, Ayano C Fiala, Gina J Agudelo, Leandro Z Dyck, Lydia Kane, Harry Douglas, Aaron Cunningham, Stephen Prendeville, Hannah Loftus, Roisin Carmody, Colleen Pierre, Philippe Kellis, Manolis Brenner, Michael Argüello, Rafael J Silva-Santos, Bruno Pennington, Daniel J Lynch, Lydia Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title | Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title_full | Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title_fullStr | Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title_full_unstemmed | Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title_short | Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments |
| title_sort | distinct metabolic programs established in the thymus control effector functions of γδ t cell subsets in tumor microenvironments |
| url | https://hdl.handle.net/1721.1/143717 |
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