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

该项目将分析调节CD4 T细胞的机制，并通常阻止免疫系统攻击我们自己身体的某些部位。控制T细胞的未知错误导致自身免疫性疾病，如1型糖尿病、多发性硬化症和甲状腺疾病，在这些疾病中，T细胞会损害或破坏重要器官。为了开发合理、具体的治疗和预防这些疾病的方法，有必要确定和了解通常控制T细胞对自身成分反应的遗传和生化机制，以及遗传缺陷如何导致这些机制崩溃。该项目的重点是确定CD4 T细胞调节如何在两个公认的自身免疫性疾病遗传易感性的例子中被破坏。自身免疫易感基因的直接作用将在负责自身免疫攻击的特定T细胞水平上确定，并在T细胞内的生化途径失调方面确定。通过确定自身免疫性疾病失调的机制和生化途径，本项目的结果将揭示理解和诊断自身免疫性疾病的靶点，并开发新的药物或疫苗，以防止T细胞破坏重要器官并治愈这些疾病。

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, 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 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 two well established examples of inherited susceptibility to autoimmune disease. The direct action of autoimmune susceptibility genes will be determined at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will reveal targets for understanding and diagnosing autoimmune diseases and for developing new drugs or or vaccines to prevent T cells damaging vital organs and cure these diseases.