IL-22 downregulates peptidylarginine deiminase-1 in human keratinocytes: adding another piece to the IL-22 puzzle in epidermal barrier formation.

Abstract

Increased presence of interleukin (IL)-22+ cells in the skin is a characteristic finding in skin barrier defects, such as atopic dermatitis (AD) and psoriasis. However, mechanistic insights 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(PAD1), enzyme that converts peptidyl-arginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of PAD1 in epidermal keratinocytes. Subsequently, the total PAD activity and the extent of protein deimination in keratinocytes treated with IL-22 was reduced together with a significant decrease in deimination of keratin 1 (KRT1) and filaggrin (FLG), both important for epidermal differentiation. Importantly, vitamin D and acitretin partly restored the PAD1 defect caused by IL-22. Collectively, we show that IL-22 downregulates deimination, thus identifying a potential target for treatment of skin barrier defects.