Activation-induced iron flux controls CD4 T cell proliferation by promoting proper IL-2R signaling and mitochondrial function

• Published in: The Journal of immunology (1950) 2020-03, Vol.204 (7), p.1708-1713
• Main Authors: Yarosz, Emily L., Ye, Chenxian, Kumar, Ajay, Black, Chauna, Choi, Eun-Kyung, Seo, Young-Ah, Chang, Cheong-Hee
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1901399

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. Here, 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-2 receptor-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-2 receptor signaling and mitochondrial function.