Genetic and molecular mechanisms dysregulating CD4 T cell tolerance in organ-specific autoimmunity

器官特异性自身免疫中 CD4 T 细胞耐受失调的遗传和分子机制

• 批准号: nhmrc : 366772
• 负责人: Prof Christopher Goodnow
• 金额: $ 38.4万
• 依托单位: Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genetic-molecular-mechanisms-specific-autoimmunity/97164
• 关键词: Genetic; molecular; mechanisms; dysregulating; CD4

This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in a well established but poorly understood example of polygenic inherited susceptibility to autoimmune disease. Polygenic diseases are those where susceptibility is inherited in a complex way involving many different genes either acting together or in opposition, and the molecular basis for this kind of inheritance is particularly poorly understood. The project will analyse the basis for this kind of inheritance pattern by analysing the direct action of diabetes susceptibility genes at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within the T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will concepts and targets for understanding and diagnosing autoimmune diseases and for developing new drugs or vaccines to prevent T cells damaging vital organs and cure these diseases.

该项目将分析调节CD4T细胞的机制，并正常阻止免疫系统攻击我们身体的某些部位。T细胞控制方面的未知错误会导致自身免疫性疾病，如1型糖尿病、多发性硬化症、爱迪生S病和甲状腺疾病，这些疾病中T细胞会损害或摧毁重要器官。为了开发合理、特异的治疗和预防这些疾病的方法，有必要识别和了解正常情况下控制T细胞对自身成分的反应的遗传和生化机制，以及遗传缺陷如何导致这些机制的破坏。该项目的重点是确定在自身免疫性疾病的多基因遗传易感性中，CD4T细胞调节是如何破坏的，但人们对此了解不多。多基因疾病是指以一种复杂的方式遗传易感性的疾病，涉及许多不同的基因共同作用或相互作用，而这种遗传的分子基础尤其鲜为人知。该项目将通过分析糖尿病易感基因在负责自身免疫攻击的特定T细胞水平上的直接作用，以及在失调的T细胞内的生化途径，来分析这种遗传模式的基础。通过确定自身免疫紊乱的机制和生化途径，该项目的结果将有助于了解和诊断自身免疫性疾病的概念和目标，以及开发防止T细胞损害重要器官和治愈这些疾病的新药或疫苗。