1. Apremilast downregulates interleukin-17 production and induces splenic regulatory B cells and regulatory T cells in imiquimod-induced psoriasiform dermatitis.
- Author
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Uchida H, Kamata M, Shimizu T, Egawa S, Ito M, Takeshima R, Mizukawa I, Watanabe A, and Tada Y
- Subjects
- Animals, Disease Models, Animal, Down-Regulation drug effects, Down-Regulation immunology, Female, Humans, Imiquimod administration & dosage, Imiquimod toxicity, Interleukin-17 metabolism, Mice, Psoriasis chemically induced, Psoriasis immunology, Psoriasis pathology, Spleen cytology, Spleen drug effects, Spleen immunology, Spleen pathology, Thalidomide pharmacology, Thalidomide therapeutic use, B-Lymphocytes, Regulatory immunology, Interleukin-17 antagonists & inhibitors, Psoriasis drug therapy, T-Lymphocytes, Regulatory immunology, Thalidomide analogs & derivatives
- Abstract
Background: Apremilast, a selective inhibitor of the enzyme phosphodiesterase 4, is efficacious for psoriasis. However, detailed in vivo effects of apremilast on psoriasis remain to be elucidated., Objective: To examine the in vivo effects of apremilast on psoriasis., Methods: Psoriasiform dermatitis was induced by applying imiquimod (IMQ) on the murine shaved back skin for six days. Mice were treated with apremilast or vehicle intraperitoneally daily., Results: Apremilast alleviated IMQ-induced psoriasiform dermatitis clinically and pathologically on days 3-6 by reducing infiltration of antigen-presenting cells and interleukin (IL)-17A-positive cells and increasing infiltration of Foxp3-postive cells into the skin on day 6, although a significant increase in IL-10 mRNA level was not observed on day 2. In addition, mRNA expression of IL-17A, IL-17F, and IL-22 was lower in the skin of IMQ-applied mice treated with apremilast than in those without apremilast on day 2, and apremilast inhibited infiltration of IL-17A-producing γδ T cells into the dermis on day 6. Furthermore, apremilast induced regulatory T cells and regulatory B cells in the spleen but not in the draining lymph nodes., Conclusion: Apremilast downregulated IL-17 production and induced splenic regulatory B cells and regulatory T cells in an IMQ-induced psoriasiform dermatitis mouse model., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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