Inhibition of IL-17–committed T cells in a murine psoriasis model by a vitamin D analogue - 07/03/18
, Teruki Dainichi, MD, PhD a, Tetsuya Honda, MD, PhD a, Atsushi Otsuka, MD, PhD a, Gyohei Egawa, MD, PhD a, Saeko Nakajima, MD, PhD a, Yoshiki Miyachi, MD, PhD b, Kenji Kabashima, MD, PhD a, c, d, ⁎ Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Psoriasis, calcipotriol, vitamin D analogue, IL-17A, IL-23, imiquimod
Abbreviations used : CAL, DC, dLN, EtOH, IMQ, LC, PE, T17, TCR
Plan
| Supported in part by Grants-in-Aid for Scientific Research from the Ministries of Education, Culture, Sports, Science and Technology, Precursory Research for Embryonic Science and Technology, and Health, Labour and Welfare of Japan and Torii Pharmaceutical. |
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| Disclosure of potential conflict of interest: N. Kusuba's institution received a grant from Torii Pharmaceutical for this work and grants from GlaxoSmithKline Japan for other works. A. Kitoh's institution received a grant from Torii Pharmaceutical for this work and received grants from the Japan Blood Products Organization, Mitsubishi Tanabe Pharma, Sanofi Japan Group, AbbVie GK, the Lydia O'leary Memorial Pias Dermatological Foundation, Actelion Pharmaceuticals Japan, and the Fujiwara Memorial Foundation for other works. T. Dainichi's institution received grants from AbbVie GK, Mitsubishi Tanabe Pharma, Sanofi Japan Group, and Novartis Pharma for other works, and the author personally received payment for lectures from Maruho, Mitsubishi Tanabe Pharma, Sanofi Japan Group, Kaken Pharmaceutical, Taiho Pharma, GlaxoSmithKline, Nihon Pharmaceutical, Novartis Pharma, and Torii Pharmaceutical. T. Honda's institution received grants from Mitsubishi Tanabe Pharma, Sanofi Japan Group, AbbVie GK, the Lydia O'leary Memorial Pias Dermatological Foundation, ROHTO Pharmaceutica, Shiseido, Novartis international AG, and Kao and payment for lectures from Novartis international AG, AbbVie GK, Sanofi Japan Group, Mitsubishi Tanabe Pharma, Janssen Pharma, Kyowa Hakko Kirin, and Torii Pharmaceutical. A. Otsuka's institution received grants and payment for lectures from Ono pharmaceutical and payment for lectures from MSD K.K., Bristol-Myers Squibb and Novartis, and GlaxoSmithKline Japan. G. Egawa's institution received grants from GlaxoSmithKline Japan and Novartis Pharma for other works. S. Nakajima's institution received grants from the Sanofi Japan Group and Kanae Foundation for the promotion of medical science. Y. Miyachi's institution received payments for lectures from Maruho, GlaxoSmithKline, POLA Pharma, Otsuka Pharmaceutical, Kinetic Concepts, Taisho Toyama Pharmaceutical, Noevir, Acseine, MSD KK, KAKEN Pharmaceutical, Shionogi, GALDERMA, Terumo Corporation, Shiseido Japan, Sato Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, and Kyowa Hakko Kirin. K. Kabashima's institution received a grant from Torii Pharmaceutical for this work; grants from Sanofi Japan Group, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, POLA Pharma, and Maruho for other works, and payment for lectures from POLA Pharma, Kyowa Hakko Kirin, Maruho, and Leo Pharma. |
Vol 141 - N° 3
P. 972 - mars 2018 Retour au numéro
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