
T-cells are a special type of white blood cells, which are essential to fight tumours, bacterial and viral infections and also important in the development of both autoimmunity and allergies. For T-cells to develop into functionally competent, mature white cells, immature cells from the bone marrow have to migrate to the supporting environment of the thymus, where they undergo a complex selection and differentiation programme. The thymus consists of various cell types, but thymic epithelial cells are the key supporting cells for T-cell development. Without thymic epithelium there is no T-cell development. Thymic epithelial cells provide several survival, and differentiation factors for immature T-cells, including the secreted glycoprotein family, Wnt. Generally, Wnt signals are known to regulate cell functions from cell proliferation through cell migration to cell differentiation. Our preliminary data shows, that in contrast to other factors secreted by the thymic epithelium, epithelial cells can also respond to Wnt signals. This suggests, that Wnt-s are important in maintenance and differentiation of the thymic epithelium arguing that Wnt-s can not only regulate T-cell development directly, but also indirectly via modulating epithelial cell survival and differentiation. Despite its importance, very little is known about the way Wnt-s influence the function of thymic epithelial cells. This project will study the effects of Wnt-s on thymic epithelial cell development and function, and will focus on one of the key enzymes, PKC. This knowledge will lead to better understanding of T-cell development, which is important in devising strategies to influence specific T-cell output as and where it becomes necessary in treatment of diseases.

T-cells are a special type of white blood cells, which are essential to fight tumours, bacterial and viral infections and also important in the development of both autoimmunity and allergies. For T-cells to develop into functionally competent, mature white cells, immature cells from the bone marrow have to migrate to the supporting environment of the thymus, where they undergo a complex selection and differentiation programme. The thymus consists of various cell types, but thymic epithelial cells are the key supporting cells for T-cell development. Without thymic epithelium there is no T-cell development. Thymic epithelial cells provide several survival, and differentiation factors for immature T-cells, including the secreted glycoprotein family, Wnt. Generally, Wnt signals are known to regulate cell functions from cell proliferation through cell migration to cell differentiation. Our preliminary data shows, that in contrast to other factors secreted by the thymic epithelium, epithelial cells can also respond to Wnt signals. This suggests, that Wnt-s are important in maintenance and differentiation of the thymic epithelium arguing that Wnt-s can not only regulate T-cell development directly, but also indirectly via modulating epithelial cell survival and differentiation. Despite its importance, very little is known about the way Wnt-s influence the function of thymic epithelial cells. This project will study the effects of Wnt-s on thymic epithelial cell development and function, and will focus on one of the key enzymes, PKC. This knowledge will lead to better understanding of T-cell development, which is important in devising strategies to influence specific T-cell output as and where it becomes necessary in treatment of diseases.
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