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.

我们的热量取决于免疫系统的正常功能。免疫系统的功能受到唯一的调节，以使其能够保持对病原体（例如病毒）的强大攻击，但仍能耐受自己的组织。尽管免疫系统的功能已广泛研究，但是导致免疫系统错误地攻击自己的身体或允许某些病毒（例如HIV）（例如HIV）的机制仍然未知。由免疫系统失调引起的80多种临床上不同的自身免疫性疾病。一些是众所周知的，包括类风湿关节炎，多发性硬化症，1型糖尿病和狼疮。其他人则不太熟悉，包括自身免疫性肝炎，Sjögren综合征，自身免疫性早期疾病和Pemphigus。同样，由于我们的免疫系统未能提供保护，因此有10种以上的慢性传染病，例如HIV和丙型肝炎病毒感染。总的来说，这些疾病困扰着英国和全球的人口估计占5％至8％。这些长期衰弱的疾病施加的社会和金融伯伦斯包括生活质量差，医疗保健成本高以及生产力的大量损失。最近，我们在一种类型的白细胞T细胞中发现了两个分子Egr2和3的独特功能，这对于防止免疫系统攻击自我组织是必不可少的，同时促进对病毒的免疫攻击。从小鼠T细胞中去除这两个分子会导致与人类狼疮疾病相似的严重自身免疫性疾病，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，并且已经发表在领先的免疫学期刊上，例如“免疫学杂志”，“实验医学杂志”和“免疫”和“免疫”。拟议的研究旨在定义EGR2和3防止T细胞攻击自我组织但增强其抗病毒功能的机制。拟议的研究的发现不仅会为免疫功能提供更好的概念理解，而且重要的是为开发自身免疫性和慢性传染病的疗法提供了新的策略。

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