Targeting New Mechanisms In The Control Of Thymus Function To Restore Balanced T-cell Production

The immune system is a mixture of cells and tissues in our body that has multiple essential functions. First, immune cells fight infection by viruses, bacteria and parasites, which are collectively called pathogens. Indeed, as scientists we have hijacked this remarkable ability of the immune system to identify and target foreign invaders by creating the process of immunization, where harmless forms of pathogens can be used as vaccines that then protect us from potentially life threatening diseases. Second, our immune systems are important in recognizing and mounting responses to tumours that form during cancer. Most recently, effective therapies for cancer treatment use approaches to boost the ability of immune cells to recognize and target cancers, which again highlights the importance of the immune system in health and disease. For all aspects of immune system function, T-cells are considered as essential orchestra conductors. T-cells are a specialized type of white blood cell with multiple functions. For example, they can can either directly kill pathogens, or help other immune cells to function. Importantly, T-cells are only made in one site in the body, an organ called the thymus. This organ lies above the heart in the chest, and its sole purpose is to support the complex process of T-cell development. As such, understanding how the thymus works is fundamentally important in understanding how our immune systems work. Without a functional thymus, the immune system is severely compromised, and we are left vulnerable to pathogens that would otherwise be innocuous. Despite the known importance of the thymus, we still do not understand how the thymus develops and functions. This limitation is a major bottleneck in being able to manipulate the immune system to generate better treatments for diseases where T-cell development is absent or reduced (immunodeficiency) or targeted against our own body (autoimmunity). In addition, as the thymus gets smaller with age, the immune system in elderly life becomes compromised. This provides multiple major obstacles. First, it limits the success of vaccination in the elderly. Second, it impacts upon the successful use of bone marrow transplantation for cancer patients, where recovery of normal immune function depends on a functional thymus. We believe that by understanding the thymus, we will be able to limit life-threatening diseases, and improve the treatment of cancer. We know that epithelial cells present in the thymus are important for its function, but we don't know how these cells work. By identifying new types of epithelial cell, we will work out which parts of the thymus are responsible for its function. In addition, by discovering how the thymus produces different types of T-cell, in both health and following bone marrow transplant, we will be able to manipulate and monitor thymus function. Through the identification of mechanisms that control the thymus in health, we will be able to identify new targets to boost thymus function in disease. Ultimately, our research will mean that we will have a far deeper understanding of the way in which an essential organ works in our immune systems, which we can then use to design better, more effective and specific therapies that correct or improve multiple immune disorders.