Journal article 135 views 30 downloads
Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
The Journal of Immunology, Volume: 212, Issue: 11, Pages: 1706 - 1713
Swansea University Authors:
Benjamin Jenkins, Nick Jones
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Copyright © 2024 by The American Association of Immunologists, Inc.
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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...
Published in: | The Journal of Immunology |
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ISSN: | 0022-1767 1550-6606 |
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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. 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.</abstract><type>Journal Article</type><journal>The Journal of Immunology</journal><volume>212</volume><journalNumber>11</journalNumber><paginationStart>1706</paginationStart><paginationEnd>1713</paginationEnd><publisher>The American Association of Immunologists</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0022-1767</issnPrint><issnElectronic>1550-6606</issnElectronic><keywords/><publishedDay>1</publishedDay><publishedMonth>6</publishedMonth><publishedYear>2024</publishedYear><publishedDate>2024-06-01</publishedDate><doi>10.4049/jimmunol.2300649</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders/><projectreference/><lastEdited>2024-06-13T14:29:01.3236054</lastEdited><Created>2024-04-16T09:38:11.1307771</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Eimear K.</firstname><surname>Ryan</surname><order>1</order></author><author><firstname>Christy</firstname><surname>Clutter</surname><orcid>0000-0001-6236-5636</orcid><order>2</order></author><author><firstname>Conor De</firstname><surname>Barra</surname><order>3</order></author><author><firstname>Benjamin</firstname><surname>Jenkins</surname><order>4</order></author><author><firstname>Simon</firstname><surname>O’Shaughnessy</surname><order>5</order></author><author><firstname>Odhrán K.</firstname><surname>Ryan</surname><orcid>0000-0003-2750-4607</orcid><order>6</order></author><author><firstname>Chloe</firstname><surname>McKenna</surname><orcid>0000-0002-3602-9855</orcid><order>7</order></author><author><firstname>Helen M.</firstname><surname>Heneghan</surname><orcid>0000-0002-2009-3406</orcid><order>8</order></author><author><firstname>Fiona</firstname><surname>Walsh</surname><orcid>0000-0003-0789-1689</orcid><order>9</order></author><author><firstname>David K.</firstname><surname>Finlay</surname><orcid>0000-0003-2716-6679</orcid><order>10</order></author><author><firstname>Linda V.</firstname><surname>Sinclair</surname><orcid>0000-0003-1248-7189</orcid><order>11</order></author><author><firstname>Nick</firstname><surname>Jones</surname><orcid>0000-0003-4846-5117</orcid><order>12</order></author><author><firstname>Daniel T.</firstname><surname>Leung</surname><orcid>0000-0001-8401-0801</orcid><order>13</order></author><author><firstname>Donal</firstname><surname>O’Shea</surname><order>14</order></author><author><firstname>Andrew E.</firstname><surname>Hogan</surname><orcid>0000-0001-5875-230x</orcid><order>15</order></author></authors><documents><document><filename>66067__30630__68b624f9d2e747fdb280410f8f4cf62f.pdf</filename><originalFilename>Final Ryan Iron MAIT Manuscript Final.pdf</originalFilename><uploaded>2024-06-13T13:49:55.7950919</uploaded><type>Output</type><contentLength>2230668</contentLength><contentType>application/pdf</contentType><version>Accepted Manuscript</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright © 2024 by The American Association of Immunologists, Inc.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807> |
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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 |
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The Journal of Immunology |
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212 |
container_issue |
11 |
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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 |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science |
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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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1801752770283307008 |
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11.021648 |