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名称（姓氏、名字、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.博士。DuSun机构/公司主管/雇主MGH/哈佛大学Andrew D.我的最终目标是获得一个学术职位，在那里我可以指导我自己的研究实验室以及教学。我特别感兴趣的是研究白细胞运输的协调，以产生适当的免疫反应。为了实现这个目标，我选择在卢斯特博士的实验室从事一个项目，这将扩大我在免疫学和研究技术方面的知识。虽然我以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，以跟上这个快速发展的领域，并向实验室和社区中许多有才华的研究人员和调查人员学习。 19. I'm sorry.姓名和学位Luster，Andrew D.，医学博士，博士20.职位/职级主任，免疫学和炎症中心。n/疾病r主任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（请勿超过所提供的空间）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分别在胸腺和外周的不同微环境中表达。SLC和ELC在胸腺的皮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的运输。此外，CCR7、CCR9及其配体在外周中的表达模式提示在成熟T细胞迁移的调节中起作用。CCR7在初始和中枢记忆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细胞区中表达。这些表达模式表明CCR7在次级淋巴器官中T细胞的保留中的作用。相反，CCR9在固有层和上皮内T细胞上表达，其配体TECK由小肠内衬的内皮细胞表达。因此，建议CCR 9具有靶向淋巴细胞迁移至小肠的功能。然而，这些建议的功能是基于相关的数据。 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。希望这些研究将阐明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（1998年12月修订版）表格第2页BB cc个人NRSA申请名称（姓、名、中间名首字母）目录=