Investigation of the early growth response gene (Egr) 2 and 3 mediated regulatory programme in T cells

T 细胞中早期生长反应基因 (Egr) 2 和 3 介导的调控程序的研究

• 批准号: MR/N00096X/1
• 负责人: Ping Wang
• 金额: $ 61.6万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN00096X%2F1
• 关键词: Investigation; early; growth; response; gene

Our heath relies on the normal function of the immune system. The function of the immune system is uniquely regulated in such a way that it can maintain a robust attack against pathogens, such as viruses, but remain tolerant of one's own tissues. Although the function of the immune system has been extensively studied, the mechanisms which cause the immune system to mistakenly attack one's own body or to permit the persistence of certain viruses, such as HIV, in our body are still unknown. More than 80 clinically distinct autoimmune diseases result from dysregulation of the immune system. Several are well known, including rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and lupus. Others are less familiar, including autoimmune hepatitis, Sjögren's syndrome, autoimmune ear disease, and pemphigus. Equally, more than 10 chronic infectious diseases, such as HIV and hepatitis C virus infection, result from a failure of our immune system to provide protection. Collectively, these diseases afflict an estimated 5 to 8 per cent of the population in the UK and worldwide. The social and financial burdens imposed by these chronic, debilitating diseases include poor quality of life, high health care costs, and substantial loss of productivity. Recently we discovered a unique function of two molecules, Egr2 and 3, in one type of white blood cells, T cells, which is essential for preventing the immune system from attacking self-tissues while promoting immune attacks on viruses. Removal of these two molecules from T cells from mice results in severe autoimmune diseases that are similar to human lupus diseases and these mice also fail to recover from virus infection. These findings were previously unknown and have been published in leading immunological journals such as 'The Journal of Immunology', 'The Journal of Experimental Medicine' and 'Immunity'. The proposed study aims to define the mechanisms by which Egr2 and 3 prevent T cells from attacking self-tissues but enhance their anti-virus function. The findings from the proposed study would not only provide a better conceptual understanding of immunological function, but importantly provide new strategies for the development of therapies for autoimmune and chronic infectious diseases.

我们的健康依赖于免疫系统的正常功能。免疫系统的功能以这样一种方式被独特地调节，即它可以保持对病原体（如病毒）的强大攻击，但对自己的组织保持耐受性。虽然免疫系统的功能已被广泛研究，但导致免疫系统错误地攻击自己的身体或允许某些病毒（如HIV）在我们体内持续存在的机制仍然未知。超过80种临床上不同的自身免疫性疾病是由免疫系统调节失调引起的。有几种是众所周知的，包括类风湿性关节炎、多发性硬化症、1型糖尿病和狼疮。其他不太熟悉，包括自身免疫性肝炎，干燥综合征，自身免疫性耳部疾病和天疱疮。同样，10多种慢性传染病，如艾滋病毒和丙型肝炎病毒感染，是由于我们的免疫系统未能提供保护造成的。总的来说，这些疾病折磨着英国和世界各地约5%至8%的人口。这些慢性、使人衰弱的疾病造成的社会和财政负担包括生活质量差、保健费用高和生产力的严重损失。最近，我们在一种白色血细胞T细胞中发现了两种分子Egr 2和3的独特功能，这对于防止免疫系统攻击自身组织，同时促进对病毒的免疫攻击至关重要。从小鼠T细胞中去除这两种分子会导致类似于人类狼疮疾病的严重自身免疫性疾病，并且这些小鼠也无法从病毒感染中恢复。这些发现以前是未知的，并已发表在领先的免疫学杂志，如“免疫学杂志”，“实验医学杂志”和“免疫”。这项研究旨在确定Egr 2和3阻止T细胞攻击自身组织但增强其抗病毒功能的机制。这项研究的结果不仅可以提供对免疫功能更好的概念性理解，而且重要的是为自身免疫性疾病和慢性感染性疾病的治疗提供了新的策略。

项目成果

Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation.

• DOI: 10.1084/jem.20160553
• 发表时间: 2017-06-05
• 期刊: The Journal of experimental medicine
• 作者: Miao T;Symonds ALJ;Singh R;Symonds JD;Ogbe A;Omodho B;Zhu B;Li S;Wang P
• 通讯作者: Wang P

Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells.

• DOI: 10.1002/iid3.210
• 发表时间: 2018-06
• 期刊: Immunity, inflammation and disease
• 作者: Omodho B;Miao T;Symonds ALJ;Singh R;Li S;Wang P
• 通讯作者: Wang P