Hedgehog signalling in gamma delta T-cell differentiation

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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, but after adolescence the thymus becomes smaller and it makes fewer T-cells and in elderly people it does not function well. This project will investigate how a rare type of T-cells called gamma delta T-cells are produced in the thymus at different life-stages. Gamma delta T cells are unusual because during development in the foetus different types of these cells are made at different times and then these different types of cell migrate to different tissues in the body, such as skin, gut, liver and lung, where they stay throughout the life span of the individual. Gamma delta cells are important at these sites to prevent infections, but they can also become over-active and cause inflammation so it is important to understand what controls them. Gamma delta cells are also made in the thymus after birth but different kinds of gamma delta T-cells are made after birth than in the foetus. This project will investigate why the thymus makes different kinds of gamma delta T-cells at different life-stages and will investigate what kinds of gamma delta cells are made in the old thymus compared to young adult thymus. In particular, we will investigate how proteins called Shh and Gli3 control gamma delta T-cell development at different life-stages.