CCR7 and CCR9 in T Cell Development and Trafficking

T 细胞发育和运输中的 CCR7 和 CCR9

• 批准号: 6585003
• 负责人: SHANNON K BROMLEY
• 金额: $ 4.16万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585003
• 关键词: T cell receptor; T lymphocyte; cell migration; genetically modified animals; intracellular transport; laboratory mouse; ligands; protein structure function; receptor expression; small intestines; thymus; vascular endothelium

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.

描述（由申请人提供）：受体CCR7和CCR9在胸腺细胞以及外周T细胞上受到动态调节。它们的配体 SLC/ELC 和 TECK 分别在胸腺和外周内不同的微环境中表达。 SLC和ELC在胸腺皮质髓质交界处的小血管上表达，而TECK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胸腺细胞亚群通过胸腺的运输。此外，CCR7、CCR9 及其外周配体的表达模式提示其在成熟 T 细胞迁移的调节中发挥作用。 CCR7 在初始记忆 T 细胞和中央记忆 T 细胞上表达，但在外周效应记忆 T 细胞上下调。 SLC和ELC在次级淋巴组织的T细胞区表达。这些表达模式表明 CCR7 在二级淋巴器官中 T 细胞保留中发挥作用。相比之下，CCR9 在固有层和上皮内 T 细胞上表达，其配体 TECK 在小肠内皮细胞上表达。因此，CCR9被认为具有靶向淋巴细胞迁移至小肠的功能。然而，这些提出的功能是基于相关数据的。 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。希望这些研究能够阐明 CCR7 和 CCR9 在胸腺细胞和外周 T 细胞运输中的体内功能。