IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes: Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation

Increased presence of IL-22(+) cells in the skin is a characteristic finding in skin barrier defects, such as psoriasis and atopic dermatitis. However, mechanistic insight into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here, we show reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of peptidylarginine deiminase 1 in epidermal keratinocytes. Subsequently, total peptidylarginine deiminase activity and extent of protein deimination in keratinocytes treated with IL-22 were reduced together with a significant decrease in deimination of keratin 1 and FLG, both important for epidermal differentiation. Vitamin D and acitretin partly restored the peptidylarginine deiminase 1 defect caused by IL-22. Collectively, we show that IL-22 downregulates deimination, thus identifying a potential target for treatment of skin barrier defects.

Automated summary

Increased presence of IL-22(+) cells in the skin is a characteristic finding in skin barrier defects. In this study, reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline, were observed in lesional psoriatic skin. IL-22 signaling was shown to suppress the expression of peptidylarginine deiminase 1 in epidermal keratinocytes, leading to a decrease in deimination of important proteins for epidermal differentiation. Vitamin D and acitretin partially restored the defect caused by IL-22. These findings identify a potential target for treatment of skin barrier defects.