CCR7 and CCR9 in T Cell Development and Trafficking

描述(申请人提供)：受体CCR7和CCR9在胸腺细胞和外周T细胞上是动态调节的。它们的配体SLC/ELC和Teck分别在胸腺和外周不同的微环境中表达。SLC和ELC表达在胸腺皮质髓质交界处的小血管上，而Teck则由皮质上皮细胞产生。CCR7在成熟的单阳性胸腺细胞上表达，而CCR9在双阳性胸腺细胞上表达上调。因此，CCR7和CCR9被认为指导这些不同的胸腺细胞亚群通过胸腺进行运输。此外，CCR7、CCR9及其配体在外周的表达模式提示在成熟T细胞迁移的调节中起作用。CCR7在幼稚和中枢记忆T细胞上表达，但在外周效应记忆T细胞上表达下调。SLC和ELC表达于次级淋巴组织的T细胞区。这些表达模式表明，CCR7在次级淋巴器官中保留T细胞方面发挥了作用。相反，CCR9表达在固有层和上皮内T细胞及其配体上，Teck表达于小肠衬里的内皮细胞。因此，CCR9被认为具有靶向淋巴细胞向小肠迁移的功能。然而，这些建议的函数是基于相关数据的。 我们将产生T细胞过度表达CCR7或CCR9的转基因小鼠。然后，我们将跟踪和分析胸腺细胞和外周T细胞的迁移。这些研究有望阐明CCR7和CCR9在胸腺细胞和外周T细胞转运中的体内功能。

DESCRIPTION (provided by the applicant): The receptors CCR7 and CCR9 are dynamically regulated on thymocytes as well as on peripheral T cells. Their ligands SLC/ELC and TECK, respectively, are expressed in distinct microenvironments within the thymus and periphery. SLC and ELC are expressed on small vessels at the corticomedullary junction of the thymus, while TECK is produced by cortical epithelial cells. CCR7 is expressed on mature single positive thymocytes, while CCR9 is up-regulated on double positive thymocytes. Thus, CCR7 and CCR9 are thought to direct the trafficking of these distinct thymocyte subpopulations through the thymus. In addition, the expression patterns of CCR7, CCR9, and their ligands in the periphery are suggestive of a role in the regulation of mature T cell migration. CCR7 is expressed on naive and central memory T cells, but is down-regulated on peripheral effector memory T cells. SLC and ELC are expressed in the T cell zone of secondary lymphoid tissues. These expression patterns suggest a role for CCR7 in the retention of T cells in secondary lymphoid organs. In contrast, CCR9 is expressed on lamina propria and intraepithelial T cells and its ligand, TECK is expressed by endothelial cells lining the small intestine. Thus, CCR9 is proposed to function in targeting lymphocyte migration to the small intestine. However, these proposed functions are based on correlative data. We will generate transgenic mice whose T cells over-express either CCR7 or CCR9. We will then track and analyze the migration of both thymocytes and peripheral T cells. It is hoped that these studies will elucidate the in vivo function of CCR7 and CCR9 in thymocyte and peripheral T cell trafficking.