Therapeutic effects of erythroid differentiation regulator 1 (Erdr1) on atopic dermatitis-like skin inflammation in NC/Nga mice

Abstract

Abstract Atopic Dermatitis (AD) is a representative chronic inflammatory skin disease. It is characterized by a defective skin barrier and dysregulation of the immune system as result of excessive Th2 immune response. IL-18, a well-known pro-inflammatory cytokine, is particularly closely associated with AD severity and IgE level in AD patients. Recent studies have been reported that erythroid differentiation regulator (Erdr1) has a negative correlation with IL-18 and exerts anti-inflammatory effects on inflammatory skin diseases, such as psoriasis, rosacea, and melanoma. In this study, to investigate whether Erdr1 has a preventive effect on AD, NC/Nga mice were used to induce AD-like skin inflammation. Then, recombinant Erdr1 (rErdr1) was administered by intraperitoneal (i.p.) injection. As results, rErdr1 administration significantly decreased the severity of AD including redness, edema, scaling, and excoriation. In addition, IgE and IL-4 production were suppressed by rErdr1 in the AD mouse model. To elucidate the related mechanisms, the expression of Th2 chemoattractants and angiogenic factor was determined. The expression of CCL17 and CCL22 was significantly lower in rErdr1-treated mice than in vehicle control-treated mice. Also, a representative angiogenic factor, VEGF expression was inhibited by rErdr1 administration. To our knowledge, this is the first evidence that rErdr1 has a preventive effect on AD based on its ability to reduce Th2 chemoattractants and angiogenesis in an AD-like mouse model. Therefore, we suggest that supplementation with rErdr1 might be an effective and improved therapeutic strategy for the treatment of AD.