T cells require Foxo1 to populate the peripheral lymphoid organs.

Forkhead (Fox) transcription factors play critical roles in leukocyte homeostasis. To study further the immunological functions of Foxo1, we generated mice that selectively lack Foxo1 in T cells (Foxo1 cKO). Although thymocyte development appeared relatively normal, Foxo1 cKO mice harbored significantly increased percentages of mature single positive T cells in the thymus as compared to wild type (WT) mice, yet possessed smaller lymph nodes and spleens that contained fewer T cells. Foxo1 cKO T cells were not more prone to apoptosis, but instead were characterized by a CD62Llo CCR7lo CD44hi surface phenotype, a poorly populated lymphoid compartment in the periphery, and were relatively refractory to TCR stimulation, all of which were associated with reduced expression of Sell, Klf2, Ccr7 and S1pr1. Thus, Foxo1 is critical for naïve T cells to populate the peripheral lymphoid organs by coordinating a molecular program that maintains homeostasis and regulates trafficking.

叉头（Fox）转录因子在白细胞内稳态中起关键作用。为了进一步研究Foxo1的免疫功能，我们培育了在T细胞中选择性缺失Foxo1的小鼠（Foxo1条件性基因敲除小鼠，Foxo1 cKO）。尽管胸腺细胞发育看起来相对正常，但与野生型（WT）小鼠相比，Foxo1 cKO小鼠胸腺中成熟单阳性T细胞的百分比显著增加，然而其淋巴结和脾脏较小，所含T细胞也较少。Foxo1 cKO T细胞并非更易发生凋亡，而是具有CD62L低表达、CCR7低表达、CD44高表达的表面表型，外周淋巴区细胞数量少，并且对T细胞受体（TCR）刺激相对不敏感，所有这些都与Sell、Klf2、Ccr7和S1pr1表达降低有关。因此，Foxo1通过协调维持内稳态和调节迁移的分子程序，对初始T细胞在周围淋巴器官中的分布至关重要。