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Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions

Eimear K. Ryan, Christy Clutter Orcid Logo, Conor De Barra, Benjamin Jenkins, Simon O’Shaughnessy, Odhrán K. Ryan Orcid Logo, Chloe McKenna Orcid Logo, Helen M. Heneghan Orcid Logo, Fiona Walsh Orcid Logo, David K. Finlay Orcid Logo, Linda V. Sinclair Orcid Logo, Nick Jones Orcid Logo, Daniel T. Leung Orcid Logo, Donal O’Shea, Andrew E. Hogan Orcid Logo

The Journal of Immunology, Volume: 212, Issue: 11, Pages: 1706 - 1713

Swansea University Authors: Benjamin Jenkins, Nick Jones Orcid Logo

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DOI (Published version): 10.4049/jimmunol.2300649

Abstract

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine producti...

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Published in: The Journal of Immunology
ISSN: 0022-1767 1550-6606
Published: The American Association of Immunologists 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa66067
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Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. 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spelling v2 66067 2024-04-16 Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions 90f7cfd66781feba615436189178a528 Benjamin Jenkins Benjamin Jenkins true false 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 2024-04-16 MEDS Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited. Journal Article The Journal of Immunology 212 11 1706 1713 The American Association of Immunologists 0022-1767 1550-6606 1 6 2024 2024-06-01 10.4049/jimmunol.2300649 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2024-06-13T14:29:01.3236054 2024-04-16T09:38:11.1307771 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Eimear K. Ryan 1 Christy Clutter 0000-0001-6236-5636 2 Conor De Barra 3 Benjamin Jenkins 4 Simon O’Shaughnessy 5 Odhrán K. Ryan 0000-0003-2750-4607 6 Chloe McKenna 0000-0002-3602-9855 7 Helen M. Heneghan 0000-0002-2009-3406 8 Fiona Walsh 0000-0003-0789-1689 9 David K. Finlay 0000-0003-2716-6679 10 Linda V. Sinclair 0000-0003-1248-7189 11 Nick Jones 0000-0003-4846-5117 12 Daniel T. Leung 0000-0001-8401-0801 13 Donal O’Shea 14 Andrew E. Hogan 0000-0001-5875-230x 15 66067__30630__68b624f9d2e747fdb280410f8f4cf62f.pdf Final Ryan Iron MAIT Manuscript Final.pdf 2024-06-13T13:49:55.7950919 Output 2230668 application/pdf Accepted Manuscript true Copyright © 2024 by The American Association of Immunologists, Inc. true eng
title Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
spellingShingle Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
Benjamin Jenkins
Nick Jones
title_short Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
title_full Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
title_fullStr Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
title_full_unstemmed Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
title_sort Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
author_id_str_mv 90f7cfd66781feba615436189178a528
0fce0f7ddbdbfeb968f4e2f1e3f86744
author_id_fullname_str_mv 90f7cfd66781feba615436189178a528_***_Benjamin Jenkins
0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones
author Benjamin Jenkins
Nick Jones
author2 Eimear K. Ryan
Christy Clutter
Conor De Barra
Benjamin Jenkins
Simon O’Shaughnessy
Odhrán K. Ryan
Chloe McKenna
Helen M. Heneghan
Fiona Walsh
David K. Finlay
Linda V. Sinclair
Nick Jones
Daniel T. Leung
Donal O’Shea
Andrew E. Hogan
format Journal article
container_title The Journal of Immunology
container_volume 212
container_issue 11
container_start_page 1706
publishDate 2024
institution Swansea University
issn 0022-1767
1550-6606
doi_str_mv 10.4049/jimmunol.2300649
publisher The American Association of Immunologists
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
document_store_str 1
active_str 0
description Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.
published_date 2024-06-01T14:29:01Z
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score 11.013148

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