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

Abstract

Beta-catenin is a central molecule in the Wnt pathway. Expression of a stable form of beta-catenin on CD4+CD25+ regulatory T (T(reg)) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable beta-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 beta-catenin-expressing CD4+CD25+ T(reg) cells were used instead of control T(reg) cells. Expression of stable beta-catenin on potentially pathogenic CD4+CD25- T cells rendered these cells anergic, and the beta-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, beta-catenin stabilization has a powerful effect on the prevention of inflammatory disease.