Regulation of mature T cell responses by the Wnt signaling pathway.

The canonical Wnt signaling pathway is evolutionarily conserved and plays key roles during development of many organ systems. This pathway utilizes TCF/LEF transcription factors, β-catenin coactivator, and TLE/GRG corepressors to achieve balanced regulation of its downstream gene expression. It is well established that several Wnt ligands and their effector proteins are crucial for normal T cell development. Recent studies have also revealed critical requirements for TCF-1 in generation and persistence of functional memory CD8(+) T cells, and in promoting Th2-differentiation and suppressing Th17-differentiation of activated CD4(+) T cells. Activation of β-catenin facilitated CD8(+) memory T cell formation, with enhanced protective capacity and extended survival of CD4(+) CD25(+) regulatory T cells. Upregulation of Wnt ligands was observed in Drosophila in response to Toll signaling as well as in mammalian dendritic cells and macrophages upon microbial stimulation. These new findings suggest that modulating the activity of Wnt pathway may be a powerful approach to enhance protective immunity and treat autoimmune diseases.