Iron is critical for mucosal-associated invariant T cell metabolism and effector functions

Abstract Mucosal Associated Invariant T (MAIT) cells are a population of innate T cells which play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both T cell receptor depedendant 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 which activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study we show that 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 MAIT cell metabolism and functionality, an axis which may have implications in conditions where iron availability is limited.