Foxo transcription factors are known to be involved in the control of immune homeostasis at least up to stage at which regulatory T (T_(reg)) cells become committed. Weiming Ouyang et al. now reveal a crucial role for Foxol in the control in mice of T_(reg) cell-dependent immune tolerance, independent of Foxo3. They propose that T_(reg) cells co-opt the evolutionary ancient Akt-Foxol signalling pathway to control a genetic program essential for the function of T_(reg) cells.
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