Inhibition of IL-17-committed T cells in a murine psoriasis model by a vitamin D analogue

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Kusuba, Nobuhiro¹  Kitoh, Akihiko¹  Dainichi, Teruki¹  Honda, Tetsuya¹  Otsuka, Atsushi¹  Egawa, Gyohei¹  Nakajima, Saeko¹  Miyachi, Yoshiki²  Kabashima, Kenji^1,3,4 

[1] Kyoto Univ, Grad Sch Med, Dept Dermatol, Kyoto, Japan

[2] ASTAR, Shiga Med Ctr Adults, Singapore, Singapore

[3] ASTAR, Singapore Immunol Network & Inst Med Biol, Singapore, Singapore

[4] Japan Sci & Technol Agcy, PRESTO, Saitama, Japan

关键词: Psoriasis;    calcipotriol;    vitamin D analogue;    IL-17A;    IL-23;    imiquimod;   

DOI  :  10.1016/j.jaci.2017.07.033

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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