Foxo: in command of T lymphocyte homeostasis and tolerance.

Foxo: in command of T lymphocyte homeostasis and tolerance.

The forkhead box O (Foxo) family of transcription factors consists of the mammalian orthologs of the Caenorhabditis elegans longevity protein Daf-16, and has an evolutionarily conserved function in the regulation of nutrient sensing and stress responses. Recent studies have shown that Foxo proteins control expression of immune system-specific genes such as Il7ra in naïve T cells and Foxp3 in regulatory T (Treg) cells, which are crucial regulators of T cell homeostasis and tolerance. These findings reveal that the ancient Foxo pathway has been co-opted to regulate highly specialized T cell activities. The Foxo pathway likely enables a diverse and self-tolerant population of T cells in the steady state, which is an important prerequisite for the establishment of a functional adaptive immune system.

叉头框O（Foxo）转录因子家族由秀丽隐杆线虫长寿蛋白Daf - 16的哺乳动物直系同源物组成，在营养感知和应激反应的调节中具有进化上保守的功能。最近的研究表明，Foxo蛋白控制免疫系统特异性基因的表达，例如在初始T细胞中的Il7ra以及在调节性T（Treg）细胞中的Foxp3，它们是T细胞稳态和耐受性的关键调节因子。这些发现揭示了古老的Foxo通路已被用来调节高度特化的T细胞活动。Foxo通路可能在稳定状态下使T细胞群体具有多样性和自身耐受性，这是建立功能性适应性免疫系统的一个重要先决条件。