Cutting Edge: Activation-Induced Iron Flux Controls CD4 T Cell Proliferation by Promoting Proper IL-2R Signaling and Mitochondrial Function.

Autor:	Yarosz EL; Immunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109., Ye C; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and., Kumar A; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and., Black C; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and., Choi EK; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109., Seo YA; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109 youngseo@umich.edu heechang@umich.edu., Chang CH; Immunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109; youngseo@umich.edu heechang@umich.edu.; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Apr 01; Vol. 204 (7), pp. 1708-1713. Date of Electronic Publication: 2020 Mar 02.
DOI:	10.4049/jimmunol.1901399
Abstrakt:	Iron has long been established as a critical mediator of T cell development and proliferation. However, the mechanisms by which iron controls CD4 T cell activation and expansion remain poorly understood. In this study, we show that stimulation of CD4 T cells from C57BL/6 mice not only decreases total and labile iron levels but also leads to changes in the expression of iron homeostatic machinery. Additionally, restraining iron availability in vitro severely inhibited CD4 T cell proliferation and cell cycle progression. Although modulating cellular iron levels increased IL-2 production by activated T lymphocytes, CD25 expression and pSTAT5 levels were decreased, indicating that iron is necessary for IL-2R-mediated signaling. We also found that iron deprivation during T cell stimulation negatively impacts mitochondrial function, which can be reversed by iron supplementation. In all, we show that iron contributes to activation-induced T cell expansion by positively regulating IL-2R signaling and mitochondrial function. (Copyright © 2020 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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