T cell and Dendritic Cell Dynamics in the Gut Mucosa

肠道粘膜中的 T 细胞和树突状细胞动力学

• 批准号: 7479647
• 负责人: Peter Velazquez
• 金额: $ 5.04万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479647
• 关键词: Antigens; Cell Communication; Cells; Defect; Dendritic Cells; Development; Disease; Failure; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; Goals; Immune; In Vitro; Inflammatory Bowel Diseases; Label; Laser Scanning Confocal Microscopy; Lymphoid Tissue; Mediating; Movement; Mucous Membrane; Nature; Onset of illness; Predisposition; Protein Subunits; Proteins; Receptor Signaling; Signal Transduction; Stimulus; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Technology; Tissues; Urination; cell motility; in vivo; migration; null mutation; response; trafficking

DESCRIPTION (provided by applicant): Immune mediated disease such as inflammatory bowel disease (IBD) is the result of the inappropriate T cell response. There are voids in our understanding of how T cells integrate g-protein mediated chemotactic and chemokinetic "go" signals with T cell antigen receptor "stop" signals. Together these signals result in the appropriate T cell response to stimuli. Using the powerful technology of intravital laser scanning confocal microscopy, along with fluorescently labeled T cells and dendritic cells (DC), we aim to define the biophysical dynamics of T-DC interactions in vivo. Next, we aim to define how defects in T cell "stop" versus "go" integration, resulting from a null mutation in the g-protein subunit G-alphai2, leads to altered T cell biophysical dynamics and therefore, susceptibility to T cell mediated IBD. Next, we aim to examine how regulatory cells may correct T cell dynamics in G-alphai2 null T cells leading to protection from disease onset and progression. The long-term goal is to therapeutically modulate T cell "stop" versus "go" signals to abrogate disease development and progression.

描述（由申请人提供）：免疫介导的疾病，如炎症性肠病（IBD）是不适当的T细胞应答的结果。我们对T细胞如何整合G蛋白介导的趋化性和趋化动力学“go”信号与T细胞抗原受体“stop”信号的理解存在空白。这些信号一起导致T细胞对刺激的适当反应。使用强大的活体激光扫描共聚焦显微镜技术，沿着荧光标记的T细胞和树突状细胞（DC），我们的目标是定义体内T-DC相互作用的生物物理动力学。接下来，我们的目标是定义由g蛋白亚基G-alpha 12中的无效突变引起的T细胞“停止”与“进行”整合中的缺陷如何导致T细胞生物物理动力学改变，并因此导致对T细胞介导的IBD的易感性。接下来，我们的目标是研究调节细胞如何纠正G-α 12无效T细胞中的T细胞动力学，从而保护免受疾病发作和进展。长期目标是治疗性调节T细胞“停止”与“进行”信号，以消除疾病的发展和进展。

项目成果

Visualization of mucosal homeostasis via single- and multiphoton intravital fluorescence microscopy.

通过单光子和多光子活体荧光显微镜观察粘膜稳态。

• DOI: 10.1189/jlb.0711344
• 发表时间: 2012
• 期刊: Journal of leukocyte biology
• 影响因子: 5.5
• 作者: Xu,Cassie;Shen,Yuelei;Littman,DanR;Dustin,MichaelL;Velazquez,Peter
• 通讯作者: Velazquez,Peter