Topical application of vitamin D3 analogue and corticosteroid to psoriasis plaques additionally depresses skin infiltration of Th17 cells and their ex vivo expansion

Publication date: Available online 11 May 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Toshiharu Fujiyama, Taisuke Ito, Takatsune Umayahara, Shigeki Ikeya, Kazuki Tatsuno, Atsuko Funakoshi, Hideo Hashizume, Yoshiki Tokura
BackgroundTopical combination with vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a Th17-mediated disorder, but the underlying mechanism remains unclear.ObjectiveWe investigated the effect of the topical applicant, focusing on the skin-infiltrating Th17 cells.MethodsIn ten patients with plaque psoriasis, calcipotriol (Cal), betamethasone dipropionate (Bet), or two-compound formulation (CB) was applied to three different psoriatic plaques with similar severity once a day for 14 days. One non-applied lesion was employed as control (Cntrl). Four-mm biopsy specimens were taken from each site, cut into two pieces, and subjected to histological examination and ex vivo expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2.ResultsClinical, histological, and IL-17A⁺ cell-infiltrate improvement was found in the order of CB>Cal>Bet>Cntrl or CB>Bet>Cal>Cntrl. The numbers of ex vivo expanded T cells were lowered by topical application of Bet and CB, and CB exhibited the most suppressive result. The numbers and frequency of Th17 cells were significantly reduced by CB and Cal, suggesting that Cal has a capacity to preferentially suppress Th17 cells. When the stocked T cells from Cntrl 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 the production of these cytokines with apoptosis.ConclusionThese findings suggest that Cal and Bet has different effects on T cells to normalize psoriatic changes with depressed Th17 cell expansion in the skin lesions.



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