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

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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.