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: 6831747
• 负责人: SHANNON K BROMLEY
• 金额: $ 4.99万
• 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/6831747
• 关键词: CCR7; CCR9; Cell; Development; Trafficking

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER NAME (Last, first, middle initial) Bromley, Shannon, K INSTITUTION MENTOR Haverford College Washington University Dr. Michael L. DusUn INSTITUTION/COMPANY SUPERVISOR/EMPLOYER MGH/Harvard Dr. Andrew D. Luster My ultimate goal is to obtain an academic position in which I can direct my own research lab as well as teach. I am particularly interested in examining the coordination of leukocyte trafficking for the generation of an appropriate immune response. In order to achieve that aim, t have chosen to pursue a project in Dr. Luster's laboratory that will broaden my knowledge of immunology and research techniques. While all of my previous research experience depended on the in vitro reconstitution of lymphocyte interactions and function, my postdoctoral training will include the in vivo analysis of leukocyte trafficking and response. I plan to immerse myself in literature in order to keep current with this rapidly progressing field and to learn from/with the many talented research fellows and investigators in the laboratory and community. _iLeJCFP]i 19. NAME AND DEGREE(S) Luster, Andrew D., M.D., Ph.D. 20. POSITION/RANK Director, Center for Immunology and Inflammato .n/Disease r Chief DRAI 21. RESEARCH INTERESTS/AREAS Chemokine Biology and Immune Response :l:_-t__,1=[o.]--mUm:To-].[O_._r_._ 22. DESCRIPTION (Do not exceed space provided) 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 upregulated 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 downregulated 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 overexpress 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. PHS 416-1 (Rev. 12/98) Form Page 2 BB cc Individual NRSA Aoolication NAME (Last, first, middle initial) r_ Table of Contents ========================================Section End===========================================

18. 奖学金培训目标和职业姓名（姓、名、中间名首字母） Bromley, Shannon, K 机构导师 哈弗福德学院 华盛顿大学 Michael L. DusUn 博士 机构/公司主管/雇主 MGH/哈佛大学 Dr. Andrew D. Luster My最终目标是获得一个学术职位，让我可以指导自己的研究实验室并教学。我对检查白细胞运输的协调以产生适当的免疫反应特别感兴趣。为了实现这一目标，我选择在 Luster 博士的实验室开展一个项目，这将拓宽我在免疫学和研究技术方面的知识。虽然我之前的所有研究经验都依赖于淋巴细胞相互作用和功能的体外重建，但我的博士后培训将包括白细胞运输和反应的体内分析。我计划沉浸在文学中，以便跟上这个快速发展的领域的步伐，并向实验室和社区的许多才华横溢的研究员和研究人员学习。 _iLeJCFP]i 19. 姓名和学位 Luster, Andrew D., M.D., Ph.D. 20. 职位/级别 免疫学和炎症中心主任 .n/疾病 r Chief DRAI 21. 研究兴趣/领域 趋化因子生物学和免疫反应 :l:_-t__,1=[o.]--mUm:To-] .[O_._r_._ 22. 描述（不要超出所提供的空间）受体 CCR7 和 CCR9 是对胸腺细胞以及外周 T 细胞进行动态调节。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 细胞上表达下调。 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。 PHS 416-1（修订版 12/98）表格第 2 页 BB cc 个人 NRSA Aoolication 姓名（姓氏、名字、中间名首字母） r_ 目录 ================== ======================章节结束============================ =================