Apremilast downregulates interleukin-17 production and induces splenic regulatory B cells and regulatory T cells in imiquimod-induced psoriasiform dermatitis.

Abstract Background Apremilast, a selective inhibitor of the enzyme phosphodiesterase 4, is efficacious for psoriasis. However, detailedin vivo effects of apremilast on psoriasis remain to be elucidated. Objective To examine thein 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 to 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-17 F, 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.