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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Institute on Aging
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Xu, Mai; Sharma, Archna; Hossain, M Zulfiquer et al. (2009) Sustained expression of pre-TCR induced beta-catenin in post-beta-selection thymocytes blocks T cell development. J Immunol 182:759-65
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Hossain, M Zulfiquer; Yu, Qing; Xu, Mai et al. (2008) ICAT expression disrupts beta-catenin-TCF interactions and impairs survival of thymocytes and activated mature T cells. Int Immunol 20:925-35