Thymic epithelial stem cell niche

The thymus is primarily responsible for generating naïve, self-tolerant T cells from hematopoietic precursors. However, deterioration of thymic function begins early in life, leading to a progressive loss in naïve T cell production, decline in immune system function and compromised immune recovery following damage such as from chemotherapy. Thymic epithelial cells (TEC), which provide most of the specialist functions required for T cell generation, are gradually lost during ageing by mechanisms not yet fully understood. We recently identified a postnatal thymic epithelial stem cell population and found a block in the generation of downstream subsets during ageing. We propose this is in part due to alterations in the surrounding fibroblasts and endothelial cells that make up the stem cell niche. In this project the phenotypic and molecular alterations in thymic fibroblast and endothelial cell subsets during ageing will be investigated.