Background

A better understanding of the means by which topical vitamin D analogues exert their therapeutic effect on psoriasis is of theoretical and practical importance.

Objective

We sought to clarify whether and how the topical vitamin D analogue calcipotriol (CAL) controls the IL-17A–mediated pathogenesis of murine psoriasis-like dermatitis in vivo.

Methods

Psoriasis-like dermatitis was induced by the topical application of an imiquimod (IMQ)–containing cream on the murine ear for 4 to 6 consecutive days. For topical CAL treatment, mice were treated daily with CAL solution on the ear before IMQ application.

Results

Mice treated topically with CAL exhibited much milder IMQ-induced psoriasis-like dermatitis compared with vehicle-treated mice, with impaired accumulation of IL-17A–committed T (T17) cells in the lesional skin. The IMQ-induced upregulation of Il12b and Il23a was marked in the epidermis and was abrogated by CAL application, suggesting CAL-mediated suppression of IL-23 expression. CAL inhibited Il12b and Il23a expression by Langerhans cells ex vivo stimulated with IMQ and CD40 cross-linking. Topical CAL also inhibited T17 cell expansion in the draining lymph nodes of IMQ-treated skin, implying a possible effect on T17 cell–mediated dermatitis at distant sites. In fact, topical CAL application on the IMQ-treated left ear resulted in amelioration of T17 cell accumulation and psoriasis-like dermatitis in the right ear subsequently treated with IMQ.

Conclusion

Topical CAL can exert its antipsoriatic effect on CAL-treated lesions and, concomitantly, distant lesions by attenuating the T17 cell accumulation in both CAL-treated lesions and draining lymph nodes.

中文翻译：

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维生素D类似物抑制小鼠牛皮癣模型中IL-17赋予的T细胞

背景

更好地理解局部用维生素D类似物对牛皮癣发挥治疗作用的方法具有理论和实践意义。

客观的

我们试图阐明是否以及如何通过局部维生素D类似物卡泊三醇（CAL）在体内控制IL-17A介导的鼠类牛皮癣样皮炎的发病机理。

方法

连续4至6天在鼠耳上局部应用含咪喹莫特（IMQ）的乳膏可诱发牛皮癣样皮炎。对于局部CAL治疗，每天使用IMQ之前，每天在耳朵上用CAL溶液治疗小鼠。

结果

与溶媒治疗的小鼠相比，用CAL局部治疗的小鼠表现出更轻的IMQ诱导的牛皮癣样皮炎，病变皮肤中IL-17A赋予的T（T17）细胞蓄积受损。IMQ诱导的Il12b和Il23a的上调在表皮中被标记并且通过CAL应用被消除，表明CAL介导的IL-23表达的抑制。CAL离体朗格汉斯细胞抑制Il12b和Il23a表达使用IMQ和CD40交联刺激。局部CAL还抑制了IMQ处理过的皮肤的引流淋巴结中的T17细胞膨胀，这暗示可能对远处的T17细胞介导的皮炎产生影响。实际上，在IMQ处理过的左耳上局部应用CAL可以改善随后用IMQ处理过的右耳中T17细胞积聚和牛皮癣样皮炎。

结论

局部CAL可以通过减轻CAL处理的病变和引流淋巴结中的T17细胞积累，对CAL处理的病变以及随之而来的远处病变发挥抗银屑病作用。