Foxa1/A2, Shh and Gli3 in T lymphocyte development

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T-cells are white blood cells that enable us to fight infectious disease by attacking infections and also by coordinating the immune response. T-cells are produced in an organ called the thymus. The thymus is essential, as people born without a thymus have no T-cells and cannot fight infectious disease. The thymus is also important because it ensures that the T-cells that are produced do not not attack our own bodies (they are tolerant to self), and it produces a type of T-cells that are required to dampen down the immune response, called regulatory T-cells. When the thymus does not not work properly, several different kinds of diseases arise: we could become immunodeficient because we do not have enough T-cells; we could develop autoimmune disease such as rheumatoid arthritis or type I diabetes, because our T-cells attack our own bodies and organs; finally, if T-cell expansion and development is not properly controlled we may develop leukaemia (blood cancer). It is very important to understand how the thymus controls the development of T-cells and how it makes T-cells tolerant to self, and produces regulatory T-cells to control the immune response. In this project we will investigate how four proteins, called Foxa1, Foxa2, Shh and Gli3 contribute to controlling how the thymus produces T-cells, how it makes the T-cells self tolerant, and how the thymus controls the production of regulatory T-cells.