Induction of plasma membrane ceramides in T cells and their role in functional paralysis

T 细胞质膜神经酰胺的诱导及其在功能麻痹中的作用

• 批准号: 172454098
• 负责人: Professorin Dr. Sibylle Schneider-Schaulies
• 金额: --
• 依托单位: Institut für Virologie und Immunbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/172454098?language=en
• 关键词: Induction; plasma; membrane; ceramides; cells

T cell paralysis is central to the generalised immunosuppression caused by measles virus (MV). At a cellular level, this is reflected by preferential formation of unstable immune synapses (IS) with MV-infected dendritic cells (DCs), which do not support sustained Ca-mobilisation and thereby, activation of scanning T cells. T cell silencing is exerted by the viral glycoprotein complex which, provided on DCs or viral particles, activates sphingomyelinases (SMases) in and membrane ceramides on T cells in a contact dependent manner. This accounts for MV-mediated physical T cell paralysis as reflected by collapse of microvillar extensions, and the inability to T cells to spread and polarise or directionally migrate on substrates. Thus, ceramides might generally modulate T cell signaling-dependent cytoskeletal dynamics which controls essential steps in their activation. We therefore aim to determine the relevance of receptorinduced ceramide membrane platforms in T cells for 1) lateral and vertical recruitment of surface receptors and signaling components, and 2) their role in T cell actin cytoskeletal remodeling in general with 3) emphasis on IS stability and efficiency and cell-cell communication, and modulations of these phenomena by the respective cellular or pathogen ligands.

T细胞麻痹是麻疹病毒（MV）引起的全身性免疫抑制的核心。在细胞水平上，这反映在与mv感染的树突状细胞（dc）优先形成不稳定免疫突触（is），这不支持持续的钙动员，从而激活扫描T细胞。T细胞沉默是由病毒糖蛋白复合物施加的，该复合物提供在dc或病毒颗粒上，以接触依赖的方式激活T细胞中的鞘磷脂酶（SMases）和膜神经酰胺。这解释了mv介导的物理T细胞瘫痪，反映在微绒毛延伸的崩溃上，以及T细胞无法在底物上扩散和极化或定向迁移。因此，神经酰胺可能通常调节T细胞信号依赖的细胞骨架动力学，控制其激活的基本步骤。因此，我们的目标是确定受体诱导的神经酰胺膜平台在T细胞中的相关性：1)表面受体和信号成分的横向和纵向募集；2)它们在T细胞肌动蛋白细胞骨架重塑中的作用；3)强调IS的稳定性、效率和细胞间通讯，以及各自的细胞或病原体配体对这些现象的调节。