Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Background: Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a T(H)17-mediated disorder, but the underlying mechanism remains unclear. Objective: We investigated the effect of this topical applicant, focusing on skin-infiltrating T(H)17 cells. Methods: In 10 patients with plaque psoriasis, calcipotriol (Cal), betamethasone dipropionate (Bet), or the calcipotriol and betamethasone dipropionate 2-compound formulation (CB) was applied to 3 different psoriatic plaques with similar severity once a day for 14 days. One nonapplied lesion was used as a control. Four-millimeter biopsy specimens were taken from each site, cut into 2 pieces, and subjected to histologic examination and ex vivo expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2. Results: Clinical, histologic, and IL-17A(+) cell-infiltrate improvement was found in the following order: CB > Cal > Bet > control or CB > Bet > Cal > control. Numbers of ex vivo expanded T cells were decreased by topical application of Bet and CB, and CB exhibited the most suppressive result. Numbers and frequencies of T(H)17 cells were significantly reduced by CB and Cal, suggesting that Cal has a capacity to preferentially suppress T(H)17 cells. When the stocked T cells from control samples were stimulated with anti-CD3 antibodies in the presence of Bet, Cal, or both, Cal downmodulated IL-17 and IFN-gamma production and tended to upregulate IL-4 and IL-6 without apoptosis, but Bet inhibited production of these cytokines with apoptosis. Conclusion: These findings suggest that Cal and Bet have different effects on T cells to normalize psoriatic changes, with decreased T(H)17 cell expansion in the skin lesions.