Regulating tolerogenic signals by inhibitory co-receptors

通过抑制性共受体调节耐受信号

• 批准号: nhmrc : 250399
• 负责人: Prof Denise Jackson
• 金额: $ 17.7万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulating-tolerogenic-signals-co-receptors/77071
• 关键词: Regulating; tolerogenic; signals; inhibitory; co

Immunoreceptors play an important role in balancing the threshold of cellular activation is critical in the immune response to tumours, pathogens or allergens, to arrest autoimmune and infectious disease and to provoke immunological memory to vaccination. We have discovered that Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1-CD31) is a new immunoreceptor, that belongs to a very important family of proteins, the Ig-ITIM superfamily which is a subset of the immunoglobulin superfamily. We wish to determine if PECAM-1 functions as an inhibitory receptor in the lymphoid microenvironment using genetically engineered mice which lack the protein. As some of the functional features may display modest features, we plan to cross the PECAM-1 deficient mice with hen egg lysozyme transgenic mice to test the importance of PECAM-1 in peripheral tolerance. We will also define its importance in T cell function. We will test if the PECAM-1 deficient mice are more susceptible to the onset of inducible autoimmunde diseases including mouse models of collagen-induced arthritis and diabetes. Finally, we will produce transgenic mice expressing normal and disabled signaling motifs of PECAM-1 to test their requirement in autoimmunity.

免疫受体在平衡细胞活化的阈值中起重要作用，细胞活化在对肿瘤、病原体或过敏原的免疫应答中至关重要，以阻止自身免疫性疾病和感染性疾病，并激发对疫苗接种的免疫记忆。血小板内皮细胞粘附分子-1（Platelet Endothelial Cell Adhesion Molecule-1，PECAM-1-CD 31）是一种新的免疫受体，属于免疫球蛋白超家族中的Ig-ITIM超家族。我们希望使用缺乏PECAM-1蛋白的基因工程小鼠来确定PECAM-1在淋巴微环境中是否作为抑制性受体发挥作用。由于一些功能特征可能显示出适度的特征，我们计划将PECAM-1缺陷小鼠与鸡蛋溶菌酶转基因小鼠杂交，以测试PECAM-1在外周耐受中的重要性。我们还将定义其在T细胞功能中的重要性。我们将测试PECAM-1缺陷小鼠是否更容易发生诱导性自身免疫疾病，包括胶原诱导性关节炎和糖尿病的小鼠模型。最后，我们将产生表达PECAM-1正常和失能信号基序的转基因小鼠，以测试它们在自身免疫中的需求。