We are interested in understanding signaling events in the thymus that regulate T cell development. Current efforts are aimed at delineating the role of evolutionarily conserved Wnt-beta-catenin-TCF pathway. To this end, we have manipulated the transcription factor TCF1 gene and the beta-catenin gene, which mediate the canonical Wnt signaling pathway. In this study we have used TCF1-deficient (TCF1-KO) mice, (beta-CAT) mice expressing transgenic beta-catenin. T cells develop in the thymus from a progenitor population that migrate via blood from the bone marrow to the thymus. Earliest thymic precursor (ETP) has been identified as giving rise to majority of developing thymocytes. In addition to conventional T cells, the thymus is the site of generation of innate immune cells including invariant natural killer T (iNKT) cells and innate-like iCD8 T cells. We have shown that TCF1 and beta-catenin control the generation both these cell types in the thymus.
|Yu, Qing; Sharma, Archna; Ghosh, Amalendu et al. (2011) T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. J Immunol 186:3946-52|