β-catenin, TCF, and ICAT in T cell development, function, and aging
dc.contributor.author | Hossain, Mohammad | |
dc.date.accessioned | 2012-02-10T19:58:03Z | |
dc.date.available | 2012-02-10T19:58:03Z | |
dc.date.issued | 2009 | |
dc.identifier.uri | http://hdl.handle.net/10713/893 | |
dc.description | University of Maryland, Baltimore. Molecular Medicine. Ph.D. 2009 | en_US |
dc.description.abstract | Both T cell factor (TCF) and beta-catenin play important roles during different stages of T cell development. Most strikingly, deletion of TCF results in a block early in development, which becomes complete with TCF-LEF double deletion. Similarly, T-cell specific deletion of beta-catenin impairs T cell development at the beta-selection checkpoint. However, in addition to working together to drive expression of beta-catenin-TCF target genes, both TCF and beta-catenin have the potential to work independently of each other. To specifically study the role of beta-catenin-TCF interactions during T cell development, function, and aging, we generated transgenic mice that express ICAT (Inhibitor of beta-Catenin and TCF), a naturally occurring inhibitor of beta-catenin-TCF interactions, in the T cell lineage. We found that disruption of beta-catenin-TCF interactions by ICAT expression impairs survival of thymocytes without significantly affecting their differentiation or proliferation. Interestingly, thymocyte aging shows signs of slowing down in ICAT-Tg mice, implicating beta-catenin-TCF interactions in normal thymic involution. We further show that beta-catenin-TCF interactions provide survival signals to activated T cells and promote differentiation of activated CD4 T cells into the default Th2 lineage. However, TCF represses Th1 differentiation independently of its interaction with beta-catenin. Finally, we show that beta-catenin expression accelerates the onset of aging in mature T cells. Collectively, these findings provide novel insights into the function of TCF and beta-catenin in T cell development, function, and aging. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | ICAT | en_US |
dc.subject | TCF | en_US |
dc.subject | Th2 differentiation | en_US |
dc.subject | thymic involution | en_US |
dc.subject.mesh | Apoptosis | en_US |
dc.subject.mesh | beta Catenin | en_US |
dc.title | β-catenin, TCF, and ICAT in T cell development, function, and aging | en_US |
dc.title.alternative | Beta-Catenin, TCF, and ICAT in T Cell Development, Function, and Aging | |
dc.type | dissertation | en_US |
dc.contributor.advisor | Sen, Jyoti, 1953- | |
dc.contributor.advisor | Livak, Ferenc | |
dc.identifier.ispublished | Yes | en_US |