CD44 MOLECULE VARIANT EXPRESSION IN AUTOIMMUNE DIABETES

描述（摘自申请人摘要） 白细胞对胰岛的侵袭及选择性免疫反应 胰岛素分泌β细胞的破坏表征了自身免疫性 胰岛素依赖型糖尿病（IDDM）。的目的 这项研究的目的是研究粘附分子CD44在细胞凋亡中的作用。 启动淋巴细胞侵入胰岛的机制， 最终破坏β细胞CD44是一种表面 与软骨连接蛋白同源的糖蛋白， 转录后修饰，具有整合 糖胺聚糖CD44分子在原发灶中存在变异， 由RNA选择性剪接产生的异构体结构 机制根据非肥胖糖尿病患者的初步结果， 小鼠（NOD），我们假设CD44亚型的一个特定亚群可能是 参与传递淋巴细胞募集到 小岛我们建议首先通过确定 CD44同种型的哪种组合由胰岛细胞表达， 不同阶段的胰岛炎二是探究表达模式 CD44变异体在胰岛浸润淋巴细胞中的表达 胰岛炎最后，我们想寻找潜在的配体， 浸润性白细胞表达的CD44变体的主要亚群。 我们希望，构成这一建议的研究将有助于阐明 负责胰岛炎和β细胞定向的分子决定因素 自身免疫

DESCRIPTION (Taken from the applicant's Abstract) Invasion of leukocytes into the pancreatic islets and the selective destruction of the insulin-secreting beta cell characterize the autoimmune disorder insulin-dependent diabetes mellitus (IDDM). The objective of this proposal is to investigate the role of the adhesion molecule CD44 in the mechanism by which lymphocyte invasion of the islet is initiated resulting in the eventual destruction of the beta cell. CD44 is a surface glycoprotein with homology to cartilage link protein, that is heavily modified post-transcriptionally, with the capability to incorporate glycoaminoglycans. The CD44 molecule presents variations in the primary structure known as isoforms, generated by a RNA alternative splicing mechanism. Based on preliminary results obtained in the non-obese diabetic mice (NOD), we hypothesize that a specific subset of CD44 isoforms may be involved in delivering key signals for lymphocyte recruitment into the islets. We propose first to extend our preliminary data by determining which combinations of CD44 isoforms are expressed by islets cells at different stages of insulitis. Second to explore the pattern of expression of CD44 variants in islet infiltrating lymphocytes at different stages of insulitis. Finally we want to search for potential ligands of the predominant subsets of CD44 variants expressed by infiltrating leukocytes. We hope that the studies that comprise this proposal will help to elucidate the molecular determinants responsible for insulitis and beta cell directed autoimmunity.