Preferential suppression of Th17 infiltrate in psoriasis plaque by topical calcipotriol/corticosteroid combination: T cell propagation study

Abstract

Topical combined therapy with vitamin D3 analogue calcipotriol and corticosteroid betamethasone dipropionate is widely used for the treatment of psoriasis. Despite its clear clinical effectiveness, the underlying mechanism remains unclear. Since Th17 cells are deeply involved in the pathogenesis of psoriasis, we investigated the effect of the topical combined applicant, focusing on the skin-infiltrating Th17 cells. In five patients with psoriasis vulgaris, calcipotriol ointment (Cal), betamethasone dipropionate ointment (Bet), or two-compound formulation (CB; Dovobet®) was applied to three different sites with similar severity of psoriatic plaques once a day for 14 days. One non-applied lesion was employed as control (Cntrl). Four-mm biopsy specimens were taken from the four sites and were cut into two pieces. One was used for histological investigation and the other half specimens are used for in vitro expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2 by using our established method. Cells were examined in their phenotype and intracellular cytokine pattern to identify Th17, Th22, Th1, and Th2 cells. Clinical improvement was found in the order of CB > Cal > Bet > Cntrl or CB > Bet > Cal > Cntrl. Consistently, the histological changes of psoriasis were normalized in the same order, and the number of the expanded T cells was high in the reversed order. CB depressed the Th17 cell number most strongly, and Cal and Bet also decreased the cell number comparably. However, the frequency of Th17 cells was more markedly reduced by Cal than Bet. These findings suggest that Cal preferentially inhibits Th17 cells, while Bet nonspecifically suppresses all T cells, presumably leading to the synergistic clinical effectiveness of CB.