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: 7338668
• 负责人: Peter Velazquez
• 金额: $ 4.88万
• 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/7338668
• 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，例如炎症性肠病（IBD）是不适当的 T 细胞反应的结果。我们对 T 细胞如何整合 g 蛋白介导的趋化和趋化动力学“go”信号与 T 细胞抗原受体“stop”信号的理解存在空白。这些信号共同导致 T 细胞对刺激做出适当的反应。利用强大的活体激光扫描共聚焦显微镜技术以及荧光标记的 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，我们的目标是确定由 g 蛋白亚基 G-alphai2 的无效突变导致的 T 细胞“停止”与“进行”整合的缺陷如何导致 T 细胞生物物理动力学改变，从而对 T 细胞介导的 IBD 易感性。接下来，我们的目标是研究调节细胞如何纠正 G-alphai2 无效 T 细胞中的 T 细胞动力学，从而防止疾病的发作和进展。长期目标是通过治疗性调节 T 细胞“停止”与“前进”信号来消除疾病的发生和进展。