Key Points TCR stimulation induces intracellular iron flux that correlates with proliferation. Iron fuels proliferation by contributing to IL-2R signaling in activated T cells. Iron is required for proper mitochondrial function after T cell activation. 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.

中文翻译：

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前沿：激活诱导的铁通量通过促进适当的 IL-2R 信号传导和线粒体功能来控制 CD4 T 细胞增殖

关键点 TCR 刺激诱导与增殖相关的细胞内铁通量。铁通过促进活化 T 细胞中的 IL-2R 信号传导来促进增殖。T 细胞激活后，正常的线粒体功能需要铁。铁长期以来被认为是 T 细胞发育和增殖的关键介质。然而，铁控制 CD4 T 细胞活化和扩增的机制仍然知之甚少。在这项研究中，我们表明刺激来自 C57BL/6 小鼠的 CD4 T 细胞不仅会降低总铁和不稳定铁水平，还会导致铁稳态机制的表达发生变化。此外，在体外抑制铁的可用性会严重抑制 CD4 T 细胞增殖和细胞周期进程。虽然调节细胞铁水平会增加活化 T 淋巴细胞产生的 IL-2，但 CD25 表达和 pSTAT5 水平降低，表明铁是 IL-2R 介导的信号传导所必需的。我们还发现，T 细胞刺激期间的铁缺乏会对线粒体功能产生负面影响，而这可以通过补充铁来逆转。总之，我们表明铁通过积极调节 IL-2R 信号传导和线粒体功能有助于激活诱导的 T 细胞扩增。