Functional Genomic Analysis of NK and NKT Cell Immune Control of Autoimmunity

NK 和 NKT 细胞免疫控制自身免疫的功能基因组分析

• 批准号: nhmrc : 137811
• 负责人: Prof Alan Baxter
• 金额: $ 46.15万
• 依托单位: James Cook University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-genomic-analysis-control-autoimmunity/81685
• 关键词: Functional; Genomic; Analysis; NK; NKT

The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reason why autoimmunity occurs is thought to be due to a failure in the mechanisms responsible for controlling such unwanted responses. Two other populations of white blood cells are involved in this regulation, termed NK and NKT cells, each of which release important cell hormones. The current project is designed to test whether defects in NK and NKT cells lead to autoimmune disease. For this purpose a special strain of mice (NOD mice) will be used. The reasons for their selection are: 1) they are highly susceptible to a range of autoimmune diseases including diabetes, lupus and anaemia, and 2) we and others have found that they are deficient in both NK and NKT cells. The proposed experiments are divided into two groups, one designed to characterise the nature of the defects in these cells and the other to identify the genes responsible for them. In this way it should be possible to shed light on the genetic basis of autoimmune diseases in general. The approach to be used involves sophisticated techniques of genetic analysis, which require production of special congenic lines of mice. These mice are like NOD mice but carry in addition to NOD genes genetic regions from a non-autoimmune strain with the potential to correct the defects in NK and NKT cells. In this way, it should be possible to pinpoint the disease susceptibility genes involved in causation of autoimmunity and to work out how they affect NK and NKT cells.

负责获得性免疫的主要白细胞是B细胞和T细胞，前者制造针对细菌等微生物的抗体，后者杀死病毒感染的细胞并帮助B细胞产生抗体。T和B细胞偶尔会攻击S体内的组织，导致自身免疫性疾病。这些疾病包括1型糖尿病、狼疮和贫血，共同代表了人类发病率和死亡率的第三大常见原因。发生自身免疫的主要原因被认为是负责控制这种不想要的反应的机制失败。另外两类白细胞也参与了这种调节，它们被称为NK细胞和NKT细胞，每一种细胞都会释放重要的细胞激素。目前的项目旨在测试NK和NKT细胞缺陷是否会导致自身免疫性疾病。为此，将使用一种特殊品系的小鼠(NOD小鼠)。选择他们的原因是：1)他们非常容易患上一系列自身免疫性疾病，包括糖尿病、狼疮和贫血；2)我们和其他人发现他们缺乏NK和NKT细胞。拟议的实验分为两组，一组旨在描述这些细胞缺陷的性质，另一组旨在确定导致缺陷的基因。通过这种方式，应该有可能从总体上阐明自身免疫性疾病的遗传基础。将要使用的方法涉及复杂的遗传分析技术，这需要生产特殊的小鼠同源品系。这些小鼠类似于NOD小鼠，但除了NOD基因外，还携带来自一种非自身免疫菌株的遗传区，有可能纠正NK和NKT细胞的缺陷。通过这种方式，应该可以确定与自身免疫相关的疾病易感基因，并找出它们如何影响NK和NKT细胞。