P24 Aminoacyl-tRNA synthetases: hidden players in psoriasis pathogenesis

Abstract Over the past two decades, immune cells have been considered the main driver of psoriasis, while keratinocytes are thought to be an executor in response to immune cells. But most recent advance indicates that keratinocytes might be also involved in the relapse of psoriasis. Our group has focused on the epidermis and its immune microenvironment for a long time. In our previous study, the proteomic analysis of the epidermis in psoriatic patients and normal individuals revealed that several members of ARSs family were significant upregulation. Aminoacyl-tRNA synthetase is a family of enzymes that play a fundamental role in protein translation. Most mammalian cytoplasmic ARSs have acquired noncatalytic domains through evolution. We investigate that glycyl-tRNA synthetase induces psoriasis-like skin lesions by promoting skin inflammation and facilitating vascular endothelial cell angiogenesis. Moreover, inhibition of epidermal isoleucyl-tRNA synthetase ameliorates psoriasis-like skin lesions via JAK2/STAT3/CXCL16 signalling pathway. Our data provide insight into the noncanonical function of aminoacyl-tRNA synthetase in the pathogenesis of psoriasis. Topical medication that blocks or reduces related members might be effective and provide an approach to control limited psoriasis.