Ryan, Eimear K. and Clutter, Christy and De Barra, Conor and Jenkins, Benjamin J. and O’Shaughnessy, Simon and Ryan, Odhrán K. and McKenna, Chloe and Heneghan, Helen M. and Walsh, Fiona and Finlay, David K. and Sinclair, Linda V. and Jones, Nicholas and Leung, Daniel T. and O’Shea, Donal and Hogan, Andrew E. (2024) Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions. The Journal of Immunology. ISSN 0022-1767

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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 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.

Item Type:	Article
Keywords:	Iron; Mucosal-Associated; Invariant T Cell Metabolism; Effector Functions;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	18390
Identification Number:	https://doi.org/10.4049/jimmunol.2300649
Depositing User:	Andrew Hogan
Date Deposited:	16 Apr 2024 11:29
Journal or Publication Title:	The Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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