Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells

β-catenin is a central molecule in the Wnt pathway. Expression of a stable form of β-catenin on CD4⁺CD25⁺ regulatory T (T_reg) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable β-catenin-expressing CD4 ⁺CD25⁺ T_reg cells outcompeted control T _reg cells in vivo, and the number of T_reg cells necessary for protection against inflammatory bowel disease could be substantially reduced when stable β-catenin-expressing CD4⁺CD25⁺ T _reg cells were used instead of control T_reg cells. Expression of stable β-catenin on potentially pathogenic CD4 ⁺CD25^- 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.