Decline in the immune system is a feature of human aging. Reduction in naive T cell repertoire to combat novel pathogens stems from decreased function of the thymus where T cells develop. Stage-specific signal transduction and gene expression, resulting from reciprocal cell-cell interactions and locally produced cytokines and hormones, is critical for T cell development. Cues from stromal cells regulate an exquisite balance of proliferation, quiescence, cell-death and cell-fate decisions in developing thymocytes. In turn, thymocytes regulate the maturation of thymic epithelial cells. Understanding this interplay at a molecular level will provide insights that might be translated into novel therapies. We have found that transgenic mice expressing beta-catenin CAT-Tg mice exhibit accelerated age-dependent thymic involution and aging. The mechanistic basis for beta-catenin-mediated thymic involution remains a major focus of our laboratory. The long-term goal of our research is to delineate molecular interactions that significantly regulate T cell development in the thymus with the aim of further defining these processes and establish protocols to boost thymic function in the elderly and immunocompromised subjects.
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