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

doi:doi:10.1038/nm1707

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.

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