Adiponectin receptor agonist adipoRon alleviates imiquimod-induced murine psoriasis

Psoriasis is a chronic inflammatory skin disease involving inflammation, immune responses and keratinocytes proliferation. It has been suggested that adiponectin/adiponectin receptor 1 (AdipoR1) signaling plays a role in regulating psoriatic skin inflammation. AdipoRon is a small molecule agonist of AdipoR1 and AdipoR2. The effect of adipoRon on psoriasis has not been elucidated. In this study, using a GEO database, we found that the expression of adiponectin was substantially decreased in skin lesions of psoriasis patients. This reduction was also validated in an imiquimod-induced psoriasis mouse model. Interestingly, we found that topical administration of adipoRon significantly ameliorated skin lesions induced by imiquimod. The critical pro-inflammatory cytokines (IL-6, IL-17A and IL-23) and the infiltration of macrophages, especially M1 macrophages were dramatically decreased while the infiltration of M2 macrophages were slightly increased in the skin lesions upon adipoRon treatment. Mechanistically, adipoRon inhibited macrophage inflammation and keratinocytes proliferation via activation of AMPK signaling pathway. Collectively, our study demonstrates that adipoRon displayed anti-inflammatory activity and anti-proliferation of keratinocytes, and attenuated psoriatic response. Activating AdipoR1 signaling pathway by adipoRon or others may represent a novel therapeutic approach to psoriasis.