Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 141, Issue 3, Pages 972-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2017.07.033
Keywords
Psoriasis; calcipotriol; vitamin D analogue; IL-17A; IL-23; imiquimod
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Precursory Research for Embryonic Science and Technology of Japan
- Ministry of Health, Labour and Welfare of Japan
- Torii Pharmaceutical
- Grants-in-Aid for Scientific Research [17K19655, 16K15548] Funding Source: KAKEN
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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.
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