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

Abstract

BackgroundPsoriasis 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. ObjectivesTo confirm reduction in adiponectin protein level in the human skin and investigate whether functional adiponectin replenishment by topical P5 application improves psoriasiform skin inflammation. MethodsAdiponectin 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. ResultsAdiponectin 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 psoriasis-related cytokines (Il17a, Il1b, Il6, and Tnfa). P5 application significantly reduced the proportion of interleukin-17A–producing γδT cells. ConclusionTransdermally deliverable adiponectin receptor 1 agonist, P5, can be a potential peptide drug to manage psoriasis by mediating the anti-psoriatic effect of adiponectin