Adiponectin-derived pentapeptide ameliorates psoriasiform skin inflammation by suppressing IL-17 production in γδT cells

Abstract

Background: Psoriasis is a common immunologic chronic skin disease that affects at least 100 million individuals worldwide. Adiponectin is associated with psoriasis and suppresses psoriasiform inflammation. Recently, a small-sized transdermally deliverable 5-mer peptide (GLYYF; P5) was discovered as a potential adiponectin receptor 1 agonist. Objectives: To confirm reduction in adiponectin protein level in the human skin and investigate whether functional adiponectin replenishment by topical P5 application improves psoriasiform skin inflammation. Methods: Adiponectin protein expression in the skin of individuals with psoriasis and normal skin was examined by immunofluorescence staining. Imiquimod-induced psoriasis-like skin inflammation was induced in wild-type (WT) and adiponectin-deficient (Adipoq(-/-)) mice. Vehicle and P5 were topically applied to the back skin and ears of mice. Histological study, reverse-transcription quantitative polymerase chain reaction, multiplex-bead array assay, and flow cytometric analysis were performed. Results: Adiponectin protein expression was downregulated both in the epidermis and dermis of psoriatic lesions as compared to that in the normal skin. Topically applied P5 attenuated the severity of imiquimod-induced psoriatic dermatitis in both WT and Adipoq(-/-) mice by decreasing the expression of psoriasisrelated cytokines (Il17a, Il1b, Il6, and Tnfa). P5 application significantly reduced the proportion of interleukin-17A-producing gamma delta T cells. Conclusion: Transdermally deliverable adiponectin receptor 1 agonist, P5, can be a potential peptide drug to manage psoriasis by mediating the anti-psoriatic effect of adiponectin (C) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.