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

Eimear K. Ryan, Christy Clutter, Conor De Barra, Benjamin J. Jenkins, Simon O'Shaughnessy, Odhrán K. Ryan, Chloe McKenna, Helen M. Heneghan, Fiona Walsh, David K. Finlay, Linda V. Sinclair, Nicholas Jones, Daniel T. Leung, Donal O'Shea, Andrew E. Hogan (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Number of pages9
JournalJournal of Immunology
Early online date15 Apr 2024
DOIs
Publication statusE-pub ahead of print - 15 Apr 2024

Fingerprint

Dive into the research topics of 'Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions'. Together they form a unique fingerprint.

Cite this