Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA.
J Immunol. 2011 Feb 1;186(3):1343-7. doi: 10.4049/jimmunol.1002238. Epub 2010 Dec 27.
The transcription factor Krüppel-like factor 2 (KLF2) controls the emigration of conventional T cells from the thymus through its regulation of the cell surface receptor S1P1. Prior to KLF2 expression, developing T cells require a positive selection signal through the TCR. However, following positive selection there are time, spatial, and maturational events that occur before KLF2 is finally upregulated and emigration occurs. We are interested in determining the signals that upregulate KLF2 and allow thymocytes to emigrate into circulation and whether they are linked to functional maturation. In endothelial cells KLF2 expression has been shown to be dependent on the mitogen-activated protein kinase ERK5. Furthermore, it has been reported that IL-7 signaling leads to the phosphorylation of ERK5. Thus, we hypothesized that IL-7R signaling through ERK5 could drive the expression of KLF2. In this study, we provide evidence that this hypothesis is incorrect. We also found that CD8 lineage specification occurred normally in the absence of IL-7R signaling, in contrast to a recently proposed model. We showed that both CD4 and CD8 T cells complete maturation and express KLF2 independently of ERK5 and IL-7.
转录因子 Krüppel 样因子 2（KLF2）通过调节细胞表面受体 S1P1 来控制常规 T 细胞从胸腺中的迁出。在 KLF2 表达之前，发育中的 T 细胞需要通过 TCR 获得阳性选择信号。然而，在阳性选择之后，会发生时间、空间和成熟事件，直到 KLF2 最终上调并发生迁移。我们有兴趣确定上调 KLF2 并允许胸腺细胞迁移到循环中的信号，以及它们是否与功能成熟相关。在内皮细胞中，已经表明 KLF2 的表达依赖于丝裂原活化蛋白激酶 ERK5。此外，据报道，IL-7 信号导致 ERK5 的磷酸化。因此，我们假设通过 ERK5 的 IL-7R 信号可以驱动 KLF2 的表达。在这项研究中，我们提供了证据表明该假设是不正确的。我们还发现，在没有 IL-7R 信号的情况下，CD8 谱系特异性正常发生，与最近提出的模型相反。我们表明，CD4 和 CD8 T 细胞均独立于 ERK5 和 IL-7 完成成熟并表达 KLF2。
