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Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses

Féaron C. Cassidy Orcid Logo, Nidhi Kedia-Mehta Orcid Logo, Ronan Bergin, Andrea Woodcock Orcid Logo, Ardena Berisha Orcid Logo, Ben Bradley, Eva Booth, Benjamin Jenkins, Odhrán K. Ryan, Nick Jones Orcid Logo, Linda V. Sinclair, Donal O’Shea, Andrew E. Hogan

Proceedings of the National Academy of Sciences, Volume: 120, Issue: 25

Swansea University Authors: Benjamin Jenkins, Nick Jones Orcid Logo

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DOI (Published version): 10.1073/pnas.2300566120

Abstract

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells which recognize a limited repertoire of ligands presented by the MHC class-I like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent...

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Published in: Proceedings of the National Academy of Sciences
ISSN: 0027-8424 1091-6490
Published: Proceedings of the National Academy of Sciences 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63935
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In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties, and rapid effector functions MAIT cells are emerging as attractive candidates for immunotherapy. In the current study, we demonstrate that MAIT cells are potent cytotoxic cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 h. However, the metabolic processes supporting rapid MAIT cell cytotoxic responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (&lt;3 h) cytokine production, as is oxidative phosphorylation. We show that MAIT cells have the machinery required to make (GYS-1) and metabolize (PYGB) glycogen and further demonstrate that that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. 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spelling v2 63935 2023-07-24 Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses 90f7cfd66781feba615436189178a528 Benjamin Jenkins Benjamin Jenkins true false 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 2023-07-24 BMS Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells which recognize a limited repertoire of ligands presented by the MHC class-I like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties, and rapid effector functions MAIT cells are emerging as attractive candidates for immunotherapy. In the current study, we demonstrate that MAIT cells are potent cytotoxic cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 h. However, the metabolic processes supporting rapid MAIT cell cytotoxic responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 h) cytokine production, as is oxidative phosphorylation. We show that MAIT cells have the machinery required to make (GYS-1) and metabolize (PYGB) glycogen and further demonstrate that that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show that glycogen-fueled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications for their use as an immunotherapeutic agent. Journal Article Proceedings of the National Academy of Sciences 120 25 Proceedings of the National Academy of Sciences 0027-8424 1091-6490 Mucosal associated invariant T cells, Metabolism, Glycogen, Cytotoxicity 20 6 2023 2023-06-20 10.1073/pnas.2300566120 http://dx.doi.org/10.1073/pnas.2300566120 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2024-02-01T16:03:49.3103323 2023-07-24T21:05:27.4362075 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Féaron C. Cassidy 0000-0003-2577-9519 1 Nidhi Kedia-Mehta 0000-0002-2863-6276 2 Ronan Bergin 3 Andrea Woodcock 0000-0002-7323-2625 4 Ardena Berisha 0000-0002-3989-4684 5 Ben Bradley 6 Eva Booth 7 Benjamin Jenkins 8 Odhrán K. Ryan 9 Nick Jones 0000-0003-4846-5117 10 Linda V. Sinclair 11 Donal O’Shea 12 Andrew E. Hogan 13 63935__28339__362cee8c45704a509a755ce537a8147f.pdf 584430_1_final_file_10196982_rv2tv7.pdf 2023-08-22T11:11:48.9304533 Output 259279 application/pdf Accepted Manuscript true 2023-12-12T00:00:00.0000000 © The Author(s) 2023. true eng
title Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
spellingShingle Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
Benjamin Jenkins
Nick Jones
title_short Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
title_full Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
title_fullStr Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
title_full_unstemmed Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
title_sort Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses
author_id_str_mv 90f7cfd66781feba615436189178a528
0fce0f7ddbdbfeb968f4e2f1e3f86744
author_id_fullname_str_mv 90f7cfd66781feba615436189178a528_***_Benjamin Jenkins
0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones
author Benjamin Jenkins
Nick Jones
author2 Féaron C. Cassidy
Nidhi Kedia-Mehta
Ronan Bergin
Andrea Woodcock
Ardena Berisha
Ben Bradley
Eva Booth
Benjamin Jenkins
Odhrán K. Ryan
Nick Jones
Linda V. Sinclair
Donal O’Shea
Andrew E. Hogan
format Journal article
container_title Proceedings of the National Academy of Sciences
container_volume 120
container_issue 25
publishDate 2023
institution Swansea University
issn 0027-8424
1091-6490
doi_str_mv 10.1073/pnas.2300566120
publisher Proceedings of the National Academy of Sciences
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
url http://dx.doi.org/10.1073/pnas.2300566120
document_store_str 1
active_str 0
description Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells which recognize a limited repertoire of ligands presented by the MHC class-I like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties, and rapid effector functions MAIT cells are emerging as attractive candidates for immunotherapy. In the current study, we demonstrate that MAIT cells are potent cytotoxic cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 h. However, the metabolic processes supporting rapid MAIT cell cytotoxic responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 h) cytokine production, as is oxidative phosphorylation. We show that MAIT cells have the machinery required to make (GYS-1) and metabolize (PYGB) glycogen and further demonstrate that that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show that glycogen-fueled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications for their use as an immunotherapeutic agent.
published_date 2023-06-20T16:03:49Z
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