Regulating tolerogenic signals by inhibitory co-receptors

免疫受体在平衡细胞激活阈值方面发挥着重要作用，在对肿瘤、病原体或过敏原的免疫反应、阻止自身免疫和感染性疾病以及激发对疫苗的免疫记忆中起着关键作用。我们发现，血小板内皮细胞黏附分子-1(PECAM-1-CD31)是一种新的免疫受体，属于一个非常重要的蛋白质家族--Ig-ITIM超家族，它是免疫球蛋白超家族的一个子集。我们希望利用缺乏PECAM-1蛋白的基因工程小鼠来确定PECAM-1是否在淋巴微环境中作为抑制性受体发挥作用。由于一些功能特征可能表现出适度的特征，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在外周免疫耐受中的重要性。我们还将确定它在T细胞功能中的重要性。我们将测试PECAM-1缺陷的小鼠是否更容易发生可诱导的自身免疫性疾病，包括胶原性关节炎和糖尿病的小鼠模型。最后，我们将制备表达PECAM-1正常和失活信号基序的转基因小鼠，以测试它们对自身免疫的需求。

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.