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Anti‐IL‐12/IL‐23p40 antibody ameliorates dermatitis and skin barrier dysfunction in mice with imiquimod‐induced psoriasis‐like dermatitis

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ABSTRACT Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system,… Click to show full abstract

ABSTRACT Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL‐23/IL‐17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti‐IL‐23 therapy is effective in psoriasis patients, and thus IL‐23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens. Dysfunction of the skin barrier is also one of the characteristics in psoriasis and is correlated with disease severity. However, there have been no reports regarding the effectiveness of antipsoriatic agents on the skin barrier dysfunction of psoriasis. In this study, we examined the effect of anti‐IL‐12/IL‐23p40 monoclonal antibody (p40 mAb) on dermatitis symptoms and skin barrier dysfunction in mice with imiquimod‐induced psoriasis‐like dermatitis. We found that p40 mAb suppressed epidermal thickness and increased transepidermal water loss (TEWL) as indicator for skin barrier function with accompanying suppression of IL‐23p19, IL‐17A, IL‐22, and keratin 16 gene expression. These results suggest that p40 mAb is not only effective against dermatitis symptoms but also skin barrier dysfunction in mice with imiquimod‐induced psoriasis‐like dermatitis. This is the first report on the effect of p40 mAb on skin barrier dysfunction related to psoriasis. Taken together, our results indicate the possibility of new insights as well as the therapeutic potential of anti‐IL‐23 for the treatment of psoriasis.

Keywords: dysfunction mice; barrier dysfunction; psoriasis; dermatitis; skin barrier

Journal Title: European Journal of Pharmacology
Year Published: 2018

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