Human epidermal Langerhans' cells are targets for the immunosuppressive macrolide tacrolimus (FK506)

Background: The immunosuppressive macrolide tacrolimus (FK506) has been sho wn to inhibit allergic contact dermatitis in animal models as well as in hu man beings. More recently, successful treatment of atopic dermatitis with a n ointment containing tacrolimus has been reported. Objectives: We explored the effects of this compound on epidermal Langerhan s' cells (LCs), which are known to play an important pathophysiologic role in inflammatory skin diseases. Methods: The expression of the intracellular FK506 binding protein (FKBP12) was monitored on freshly isolated and cultured epidermal LCs. Phenotyping and functional exploration of LCs treated with different concentrations of tacrolimus and beta -methasone valerate (beta Mv) were performed. Results: FKBP12 is expressed in freshly isolated LCs but is lost while they are maturating into mature dendritic cells. Tacrolimus inhibited the expre ssion of IL-2R (CD25) and of the costimulatory molecules CD80 (B7.1) and CD 40, Expression of MHC class I and II was also affected, whereas (3D86 (B7.2 ) expression was not altered. In contrast, beta Mv strongly increased the e xpression of CD25. Paradoxically, while decreasing CD40 and MHC class I exp ression, beta Mv significantly increased the expression of MHC class II, CD 80, and CD86 on cultured LCs but impaired their allostimulatory activity. T acrolimus was about 100 times more potent than beta Mv at inhibiting LC sti mulatory function. Conclusion: Tacrolimus can exert immunopharmacologic alterations on LCs, wh ich may account, at least in part, for the therapeutic effect of this compo und in eczematous skin diseases.