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

Abstract

Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a TH17-mediated disorder, but the underlying mechanism remains unclear. We investigated the effect of this topical applicant, focusing on skin-infiltrating TH17cells. 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 14days. 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 exvivo expansion of skin-infiltrating Tcells with anti-CD3/CD28 antibodies and IL-2. 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 exvivo expanded Tcells were decreased by topical application of Bet and CB, and CB exhibited the most suppressive result. Numbers and frequencies of TH17cells were significantly reduced by CB and Cal, suggesting that Cal has a capacity to preferentially suppress TH17cells. When the stocked Tcells from control samples were stimulated with anti-CD3 antibodies in the presence of Bet, Cal, or both, Cal downmodulated IL-17 and IFN-γ production and tended to upregulate IL-4 and IL-6 without apoptosis, but Bet inhibited production of these cytokines with apoptosis. These findings suggest that Cal and Bet have different effects on Tcells to normalize psoriatic changes, with decreased TH17cell expansion in the skin lesions.