Erdr1 is a potential therapeutic molecule in inflammatory skin disease, psoriasis

Abstract

Abstract Psoriasis is a common skin disease accompanied by chronic inflammation. Pro-inflammatory cytokines are increased in psoriatic lesional skin and have important roles in psoriasis pathogenesis. Especially, as a representative pro-inflammatory cytokine, IL-18 has been known as a biomarker for psoriasis activity. In previous studies, erythroid differentiation regulator 1 (Erdr1) was shown to have a negative correlation with IL-18 in several inflammatory skin diseases such as melanoma and rosacea, suggesting the opposite effects with IL-18. The present study investigated whether Erdr1 in negatively regulated by IL-18 in human keratinocytes in vitro and the level of cutaneous expression of Erdr1 was compared in skin tissues from psoriasis patients and healthy donors. Erdr1 expression was significantly reduced in psoriatic lesional skin whereas enhanced IL-18 expression. Based on the negative correlation, It was hypothesized that Erdr1 may exert anti-inflammatory effects in contrast to the pro-inflammatory effect of IL-18. To investigate the anti-inflammatory effects of Erdr1 in psoriasis, recombinant Erdr1 was injected intraperitoneally into a psoriasis mouse model. Recombinant Erdr1 (rErdr1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers. Additionally, rErdr1 inhibits Th17 cell distribution in psoriatic lesional skin through regulation of CCL20 expression. Taken together, this results provides the first clinical evidence that Erdr1 is downregulated in lesional skin and acts as a novel regulator for psoriasis pathogenesis which can be a potential therapeutic molecule.