Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1)
Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1)
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DOI：
10.1093/intimm/dxl151
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Offner, Halina
中科院分区：
文献类型：
--
作者：
Polanczyk, Magdalena J.;Hopke, Corwyn;Offner, Halina
雌激素[17-β-雌二醇（E2）]是FoxP 3+调节性T细胞（Treg）区室的有效驱动因子。最近，TcB的进一步特征在于负性共刺激分子程序性死亡-1（PD-1）的细胞内表达。为了阐明PD-1与FoxP 3在E2增强的Treg抑制中的作用，我们评估了野生型雌激素受体敲除（ERKO）小鼠和PD-1 KO小鼠中的标志物和功能抑制。我们证明了细胞内PD-1表达也是E2敏感的，因为E2处理增加了CD 4 + FoxP 3+细胞中的细胞内PD-1水平，并且ERKO小鼠中的PD-1表达和Treg抑制减少。令人惊讶的是，PD-1 KO小鼠保留了正常水平的FoxP 3表达，但来自这些小鼠的TcR缺乏功能抑制。然而，PD-1 KO小鼠的E2预处理部分恢复了功能性Treg抑制，而没有增强FoxP 3表达。因此，在没有E2预处理的免疫小鼠中，功能性Treg抑制与PD-1表达比与FoxP 3表达更密切相关。然而，尽管增强的PD-1表达是E2依赖性的，但在不存在PD-1的情况下，E2预处理仍然增强了功能抑制。这些数据清楚地表明，E2可以影响影响Treg抑制的多种调控元件，包括PD-1依赖性和PD-1非依赖性途径。
Estrogen [17-beta-estradiol (E2)] is a potent driver of the FoxP3+ regulatory T cell (Treg) compartment. Recently, Tregs were further characterized by intracellular expression of the negative co-stimulatory molecule, programmed death-1 (PD-1). To clarify the role of PD-1 versus FoxP3 in E2-enhanced Treg suppression, we evaluated both markers and functional suppression in wild-type, estrogen receptor knockout (ERKO) mice and PD-1 KO mice. We demonstrate that intracellular PD-1 expression is also E2 sensitive, since E2 treatment increased intracellular PD-1 levels in CD4+FoxP3+ cells, and PD-1 expression and Treg suppression were reduced in ERKO mice. Surprisingly, PD-1 KO mice retained normal levels of FoxP3 expression, but Tregs from these mice lacked functional suppression. However, E2 pre-treatment of PD-1 KO mice partially restored functional Treg suppression without enhancing FoxP3 expression. Thus, functional Treg suppression in immunized mice without E2 pre-treatment was more closely linked to PD-1 expression than to FoxP3 expression. However, although enhanced PD-1 expression was E2 dependent, functional suppression was still enhanced by E2 pre-treatment in the absence of PD-1. These data clearly demonstrate that E2 can affect multiple regulatory elements that influence Treg suppression, including both PD-1-dependent and PD-1-independent pathways.