Abstract

β-catenin is a central molecule in the Wnt pathway. Expression of a stable form of β-catenin on CD4+CD25+ regulatory T (Treg) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable β-catenin–expressing CD4+CD25+ Treg cells outcompeted control Treg cells in vivo, and the number of Treg cells necessary for protection against inflammatory bowel disease could be substantially reduced when stable β-catenin–expressing CD4+CD25+ Treg cells were used instead of control Treg cells. Expression of stable β-catenin on potentially pathogenic CD4+CD25|[minus]| T cells rendered these cells anergic, and the β-catenin–mediated induction of anergy occurred even in Foxp3-deficient T cells. Thus, through enhanced survival of existing regulatory T cells, and through induction of unresponsiveness in precursors of T effector cells, β-catenin stabilization has a powerful effect on the prevention of inflammatory disease.