Intravital Imaging of Type I Diabetes

I 型糖尿病的活体成像

基本信息

批准号：
8690037
负责人：
ALEXANDER V CHERVONSKY
金额：
$ 33.93万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8690037
关键词：
Abbreviations Abdomen Ablation Address Antigens Autoimmune Process Autoimmunity Bypass CD8B1 gene Catalytic Domain Cells Clinical Cross Presentation Data Dendritic Cells Developed Countries Development Diabetes Mellitus Disease Disease Progression Electronics Endothelial Cells Erythrocytes Event Glucose-6-Phosphate Goals Hand Homing Image Immune system In Vitro Inbred NOD Mice Incidence Individual Infiltration Inflammation Injection of therapeutic agent Insulin Insulin-Dependent Diabetes Mellitus Knowledge Link Methods Microscopy Molecular Mus Myotonic Dystrophy Natural regeneration Organ Pancreas Peptides Phosphotransferases Printing Proteins Protocols documentation Rattus Research Research Personnel Role Solutions Staging Study Section System T-Lymphocyte Techniques Testing Therapeutic Intervention Time Time Study United States National Institutes of Health Vascular Endothelium autoreactive T cell base cell type cyanine in vivo intravital imaging intravital microscopy islet movie novel novel strategies postcapillary venule programs promoter research study rhodamine isothiocyanate tetramethylrhodamine isothiocyanate trafficking

项目摘要

DESCRIPTION (provided by applicant): Three major events happen in organ-specific autoimmunity during disease progression: autoreactive T cells are generated (I), they traffic to the target organ (II), and they destroy the organ (III). Type 1 diabetes (T1D) is a clear example of such a disease. Its incidence is on the rise in developed countries, and the most efficient therapy for T1D is still the provision of insulin. We have been focusing on the studies of T cell homing to the insulin-producing islets, combining in vivo and in vitro approaches for tracing T cells and searching for molecular clues to what drives T cells to the islets. The goal of these studies is to find targets for blocking homing of T cells for therapeutic intervention in T1D. We came to realization that progress in the field was hampered by the inability to follow the fate of individual islets during T cell attack. Clearly, should we have had this possibility in hand, we would progress much faster in understanding the rules of T cell infiltration, and also in following the fate of 2 cells after T cell ablation and test 2 cell regeneration protocols. To achieve these goals, we came up with a simple solution: an abdominal window allowing intravital microscopy (AWIM). We perfected the technique to the point where we can comfortably address many issues related to T cell homing and islet destruction/regeneration. We also will employ a novel whole organ imaging approach to delineate the global features of inflammation in the pancreas during T1D development. Accordingly, we will pursue the following Specific Aims. Specific Aim 1. Further delineate the role of cross-presentation in homing of T cells. Specific Aim 2. Study the homing of naturally activated T cells to the pancreas. .

描述（由申请人提供）：在疾病进展过程中，器官特异性自身免疫会发生三个主要事件：产生自身反应性T细胞（I），它们运输到靶器官（II），并破坏器官（III）。 1 型糖尿病 (T1D) 就是此类疾病的一个明显例子。在发达国家，其发病率呈上升趋势，而治疗T1D最有效的疗法仍然是提供胰岛素。我们一直专注于 T 细胞归巢到产生胰岛素的胰岛的研究，结合体内和体外方法来追踪 T 细胞，并寻找驱动 T 细胞到达胰岛的分子线索。这些研究的目标是寻找阻断 T 细胞归巢的靶标，以用于 T1D 的治疗干预。我们逐渐意识到，由于无法追踪 T 细胞攻击过程中单个胰岛的命运，该领域的进展受到阻碍。显然，如果我们掌握了这种可能性，我们在理解 T 细胞浸润规则以及跟踪 T 细胞消融后 2 个细胞的命运和测试 2 个细胞再生方案方面会取得更快的进展。为了实现这些目标，我们提出了一个简单的解决方案：允许活体显微镜检查（AWIM）的腹窗。我们完善了该技术，可以轻松解决与 T 细胞归巢和胰岛破坏/再生相关的许多问题。我们还将采用一种新颖的全器官成像方法来描绘 T1D 发展过程中胰腺炎症的整体特征。因此，我们将追求以下具体目标。具体目标 1. 进一步阐明交叉呈递在 T 细胞归巢中的作用。具体目标 2. 研究自然激活的 T 细胞归巢至胰腺。。