Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of T_H17 cells and their ex vivo expansion

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• 作者：Toshiharu Fujiyama ; MD ; PhD^a ; ^{fujiyama@hama-med.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Taisuke Ito ; MD ; PhD^a ; Takatsune Umayahara ; MD^a ; Shigeki Ikeya ; MD^a ; Kazuki Tatsuno ; MD^a ; Atsuko Funakoshi ; PhD^a ; Hideo Hashizume ; MD ; PhD^b ; Yoshiki Tokura ; MD ; PhD^a
• 关键词：psoriasis ; IL-17A ; Th17 ; vitamin D ; corticosteroid
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：138
• 期：2
• 页码：517-528.e5
• 全文大小：4234 K

文摘

Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a T_H17-mediated disorder, but the underlying mechanism remains unclear.

Objective

We investigated the effect of this topical applicant, focusing on skin-infiltrating T_H17 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_H17 cells were significantly reduced by CB and Cal, suggesting that Cal has a capacity to preferentially suppress T_H17 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-γ 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_H17 cell expansion in the skin lesions.