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

被引:2
作者
Ryan, Eimear K. [1 ]
Clutter, Christy [2 ,3 ]
De Barra, Conor [1 ]
Jenkins, Benjamin J. [4 ]
O'Shaughnessy, Simon [5 ]
Ryan, Odhran K. [1 ,6 ]
Mckenna, Chloe
Heneghan, Helen M. [6 ]
Walsh, Fiona [1 ]
Finlay, David K. [5 ,7 ]
V. Sinclair, Linda [8 ]
Jones, Nicholas [4 ]
Leung, Daniel T. [2 ,3 ]
O'Shea, Donal [1 ,6 ]
Hogan, Andrew E. [1 ]
机构
[1] Maynooth Univ, Human Hlth Res Inst, Maynooth, Kildare, Ireland
[2] Univ Utah, Sch Med, Dept Internal Med, Div Infect Dis, Salt Lake City, UT USA
[3] Univ Utah, Sch Med, Dept Med, Div Cardiol, Salt Lake City, UT USA
[4] Swansea Univ Med Sch, Inst Life Sci, Swansea, Wales
[5] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Dublin, Ireland
[6] Univ Coll Dublin, Dublin, Ireland
[7] Trinity Coll Dublin, Sch Med, Dublin, Ireland
[8] Univ Dundee, Sch Life Sci, Div Cell Signalling & Immunol, Dundee, Scotland
基金
爱尔兰科学基金会;
关键词
TRANSFERRIN RECEPTOR; IMMUNE-RESPONSES; HYPOFERREMIA; ACQUISITION;
D O I
10.4049/jimmunol.2300649
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. The Journal of Immunology, 2024, 212: 1706-1713.- 1713.
引用
收藏
页码:1706 / 1713
页数:9
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