Source:Journal of Allergy and Clinical Immunology
Author(s): Nobuhiro Kusuba, Akihiko Kitoh, Teruki Dainichi, Tetsuya Honda, Atsushi Otsuka, Gyohei Egawa, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
BackgroundA better understanding of the means by which topical vitamin D analogues exert their therapeutic effect on psoriasis is of theoretical and practical importance.ObjectiveWe 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.MethodsPsoriasis-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.ResultsMice 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.ConclusionTopical 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.
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