T cell and Dendritic Cell Dynamics in the Gut Mucosa

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“去”信号与T细胞抗原受体“停止”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，我们的目标是定义由g蛋白亚基g- α 2的零突变引起的T细胞“停止”与“继续”整合的缺陷如何导致T细胞生物物理动力学的改变，从而导致对T细胞介导的IBD的易感性。接下来，我们的目标是研究调节性细胞如何在G-alphai2缺失的T细胞中纠正T细胞动力学，从而防止疾病的发生和进展。长期目标是治疗性地调节T细胞“停止”和“继续”信号，以消除疾病的发展和进展。

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.