Recently, we have demonstrated that T helper cell differentiation is regulated by beta-catenin and TCF1. We show that TCF1 negatively regulates IFN-gamma expression and promotes skewing toward Th1 lineage, while beta-catenin and TCF1 together work to induce IL-4 production thereby promoting Th2 fate. We have also found that TCF1 negatively regulates expression of several inflammatory cytokines including IL-17 and IL-10. In the future, we will use well-established mouse models to evaluate the effect of manipulating the beta-catenin-TCF1 signaling pathway in pathogenesis of asthma and infections such as T. muris or Leishmania. Together, these studies may provide insight in the development of bio-medical tools to combat T-helper cell-dependent diseases in humans. We have also found that CD8 memory-like cells are generated in the thymus in the absence of antigen challenge when expression of beta-catenin is increased in developing thymocytes. Generation of CD8 memory-like cells coincides with increase in a subset of thymocytes expressing the transcription factor PLZF and requires IL-4 produced by PLZF-expressing cells. Interestingly, CD8 memory-like cells that develop in the absence of antigen challenge are functional. They produce hight levels of interferon-gamma and provide protective anti-tumor immunity. a paper describing these results is being submitted for publication.
