Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
基本信息
- 批准号:7623199
- 负责人:
- 金额:$ 37.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-06-01 至 2012-05-31
- 项目状态:已结题
- 来源:
- 关键词:Activated LymphocyteAddressAustraliaB-LymphocytesBloodBlood CirculationCataractCell physiologyCellsClinicalClinical TrialsCollaborationsComplexDefectDevelopmentEffector CellExhibitsG Protein-Coupled Receptor GenesGeneticImageImmunologic SurveillanceImmunosuppressionImmunosuppressive AgentsIntegral Membrane ProteinLymphocyteLymphocyte ActivationLymphocyte FunctionLymphoidMapsMediatingMolecularMultiple SclerosisMusMutant Strains MiceOrganPatientsProductionRegulationRoleSphingosine-1-Phosphate ReceptorT-LymphocyteTestingThymus GlandTissuesTransplantationWorkgenetic analysisin vivolymph nodesnovelsmall moleculetrafficking
项目摘要
DESCRIPTION (provided by applicant): T and B cell egress from lymphoid organs is necessary for immune surveillance and effector cell function. Work over the last 25 years has provided a detailed cellular and molecular picture for how cells enter tissues from the blood. By contrast, very little has been defined about how cells exit tissues and return to circulation. The clinical importance of lymphocyte egress and lymphocyte recirculation has been revealed by the finding that the immunosuppressive molecule, FTY720, acts by inhibiting egress from lymphoid organs. Work over the last five years has established a critical role for S1P receptor-1 (S1P1) in lymphocyte egress from lymphoid organs. S1P1 has also been found to be a control point for egress regulation. The lymphocyte activation marker, CD69, acts as a negative regulator of S1P1 and lymphocyte egress. However, the mechanism by which lymphocyte S1P1 promotes egress, and the mode of CD69 mediated regulation of S1P1 remain undefined. This proposal will address the cellular and molecular requirements for lymphocyte egress and mechanisms associated with egress regulation through three specific aims. The first Aim will use a combination of cellular and multiphoton imaging approaches to characterize the S1P1-dependent step in lymphocyte egress from lymph nodes. Aim 2 will focus on determining the mechanism of CD69 mediated inhibition of S1P1 function and lymphocyte egress. The final Aim will use genetic approaches to identify additional molecules required for lymphocyte egress. This aim will build upon a collaboration with Christopher Goodnow in Australia to identify and characterize mutant mouse lines that exhibit alterations in lymphocyte trafficking. As part of this effort we will fine map and characterize the locus responsible for the thymic egress defect in Cataract Shionogi (CTS) mice. The information obtained through these studies should point to new targets for the development of immunomodulatory molecules.
描述(由申请方提供):T和B细胞从淋巴器官中排出对于免疫监视和效应细胞功能是必要的。过去25年的工作为细胞如何从血液进入组织提供了详细的细胞和分子图像。相比之下,关于细胞如何离开组织并返回循环的定义很少。免疫抑制分子FTY 720通过抑制淋巴器官的排出而起作用,这一发现揭示了淋巴细胞排出和淋巴细胞再循环的临床重要性。过去五年的工作已经确定了S1 P受体-1(S1 P1)在淋巴细胞从淋巴器官排出中的关键作用。S1 P1也被发现是出口调节的控制点。淋巴细胞活化标志物CD 69作为S1 P1和淋巴细胞排出的负调节剂。然而,淋巴细胞S1 P1促进出口的机制,以及CD 69介导的S1 P1调节的模式仍然不确定。该提案将通过三个具体目标解决淋巴细胞流出的细胞和分子要求以及与流出调节相关的机制。第一个目标将使用细胞和多光子成像方法的组合来表征淋巴细胞从淋巴结中流出的S1 P1依赖性步骤。目的二是探讨CD 69介导的S1 P1功能抑制和淋巴细胞外排的机制。最后的目标将使用遗传方法来确定淋巴细胞出口所需的其他分子。这一目标将建立在与澳大利亚Christopher Goodnow合作的基础上,以识别和表征在淋巴细胞运输中表现出改变的突变小鼠品系。作为这项工作的一部分,我们将精细映射和表征的位点负责胸腺出口缺陷的白内障Shionogi(CTS)小鼠。通过这些研究获得的信息应该指向免疫调节分子开发的新靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jason G Cyster其他文献
Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces
在没有剪切力的情况下,淋巴结趋化因子促进持续的 T 淋巴细胞运动而不触发稳定的整合素黏附性。
- DOI:
10.1038/ni1499 - 发表时间:
2007-08-26 - 期刊:
- 影响因子:27.600
- 作者:
Eilon Woolf;Irina Grigorova;Adi Sagiv;Valentin Grabovsky;Sara W Feigelson;Ziv Shulman;Tanja Hartmann;Michael Sixt;Jason G Cyster;Ronen Alon - 通讯作者:
Ronen Alon
The sphingosine 1-phosphate receptor S1P2 maintains the homeostasis of germinal center B cells and promotes niche confinement
鞘氨醇-1-磷酸受体 S1P2 维持生发中心 B 细胞的内环境稳定并促进小生境限制
- DOI:
10.1038/ni.2047 - 发表时间:
2011-06-05 - 期刊:
- 影响因子:27.600
- 作者:
Jesse A Green;Kazuhiro Suzuki;Bryan Cho;L David Willison;Daniel Palmer;Christopher D C Allen;Timothy H Schmidt;Ying Xu;Richard L Proia;Shaun R Coughlin;Jason G Cyster - 通讯作者:
Jason G Cyster
B cell follicles and antigen encounters of the third kind
B 细胞滤泡与第三种抗原相遇
- DOI:
10.1038/ni.1946 - 发表时间:
2010-10-19 - 期刊:
- 影响因子:27.600
- 作者:
Jason G Cyster - 通讯作者:
Jason G Cyster
Finding a way out: lymphocyte egress from lymphoid organs
寻找出路:淋巴细胞从淋巴器官流出
- DOI:
10.1038/ni1545 - 发表时间:
2007-11-16 - 期刊:
- 影响因子:27.600
- 作者:
Susan R Schwab;Jason G Cyster - 通讯作者:
Jason G Cyster
Jason G Cyster的其他文献
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{{ truncateString('Jason G Cyster', 18)}}的其他基金
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
8079711 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
8462890 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
7298060 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
7812261 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
9066060 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
8662682 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
Cellular and Genetic Analysis of Lymphocyte Egress
淋巴细胞排出的细胞和遗传分析
- 批准号:
8387692 - 财政年份:2007
- 资助金额:
$ 37.25万 - 项目类别:
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