Anti-IL-17A and IL-23p19 antibodies but not anti-TNFα antibody induce expansion of regulatory T cells and restoration of their suppressive function in imiquimod-induced psoriasiform dermatitis

Background: Psoriasis is a chronic inflammatory skin disease. Anti-TNF alpha, IL-17A and IL-23p19 antibodies are effective for psoriasis. However, the contribution of regulatory T cells (Treg) in their effectiveness remains to be elucidated. Objective: We investigated the effects of TNF alpha, IL-17A and IL-23p19 inhibition on Tregs in imiquimod-induced psoriasiform dermatitis. Methods: Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Mice were treated with anti-TNF alpha, IL-17A or IL-23p19 monoclonal antibodies every other day from one day before imiquimod application. Results: Administration of anti-TNF alpha, IL-17A or IL-23p19 antibodies improved the clinical score and downregulated Th17-related cytokines and chemokines, while IL-23p19 antibodies upregulated IL-10 mRNA expression. Anti-IL-17A or IL-23p19 antibody-treated imiquimod-applied mice showed a significant increase in the number of Foxp3(+) IL-10(+) Tregs. Recipient mice adoptively transferred with Tregs derived from donor mice treated with antibodies demonstrated clinical and pathological improvement in imiquimod-induced psoriasiform dermatitis. Anti-IL-17A or IL-23p19 antibody-induced Tregs significantly increased the number of Foxp3(+) cells and IL-10 expression in imiquimod-induced psoriasiform dermatitis in recipient mice but anti-TNF alpha antibody-induced Tregs did not. Conclusion: Anti-IL-17A or IL-23p19 antibody inhibits the IL-17/IL-23 signaling pathway, and induces expansion of Tregs and their suppressive capacity in imiquimod-induced psoriasiform dermatitis. (C) 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.