Alloferon and IL-22 receptor expression regulation on the pathogenesis of imiquimod-induced psoriasis

Psoriasis is an immune-mediated inflammatory skin disease. IL-22, a proinflammatory cytokine, is implicated in psoriasis pathogenesis; however, there is currently no established biological treatment targeting IL-22 or its receptor, IL-22R alpha. Alloferon is a short peptide that has an antiinflammatory effect on skin disorders; however, little is known about its anti-inflammatory activity in psoriasis. We investigated the regulatory role of alloferon in the development of psoriasis in an imiquimod (IMQ)-induced psoriasis model through the regulation of IL-22R alpha expression. The expression of IL-22R alpha was analyzed by immunofluorescence staining in primary human keratinocytes. The effect of alloferon on the development of psoriasis was investigated in IMQ-induced wild-type and IL-22R alpha KO mice. We found that alloferon decreased the expression of IL-22R alpha in psoriasis-like keratinocytes treated with TNF-alpha, while epidermal hyperplasia was observed in IMQ-induced wild-type and IL-22R alpha KO mice. In addition, the expression of IL-1 beta, IL-19, and IL-33 was suppressed when IL-22R alpha KO mice were treated with alloferon. The findings of this study indicate that alloferon could be an effective potential drug for the treatment of psoriasis by interrupting IL-22 signaling and factors related to skin inflammation.