Effects and mechanisms of tacrolimus on development of murine Th17 cells.

Tacrolimus (Tac, FK506) is a widely used T-cell-targeted immunosuppression drug known as a calcineurin inhibitor. However, its pharmacologic effects on T-helper type 17 (Th17) cells have not been fully elucidated. Herein, we demonstrate that Tac inhibits Th17 cell differentiation and proliferation, and expression of IL-17 messenger RNA. The proposed mechanism is that Tac inhibits calcineurin and T-cell receptor stimulation-induced cell division. Because Th17 cells participate in allograft rejection, the results of the present study suggest a novel model of immunosuppression effects of Tac. In addition, they provide further implications for the therapeutic immunosuppression effects of Tac on allograft rejection.