The neuro-immune cytokine interleukin 31 (IL-31) signals through the heterodimeric receptor IL-31RA/OSMRB. IL-31 is a key mediator of the pathophysiology of atopic dermatitis and prurigo nodularis directly impacting pruritus, inflammation, epidermal differentiation and skin barrier function. While IL-31RA expression is found on many cell types, IL-31 activation of keratinocytes leads to dysregulated differentiation, induction of pro-inflammatory responses and expression of pruritic mediators. However, the regulation of IL-31RA in these cells is not well known.
Through in silico analysis of gene expression across 118 keratinocyte microarray samples, we investigated the regulatory program that modulates the expression of IL-31RA in keratinocytes. We identified a module of 273 IL-31RA-correlated genes. Genes most strongly correlated with IL-31RA expression include BCLAF1, PLSCR4, LIPR1 and SLC39A10. Gene ontology term enrichment analysis of the module genes indicates that IL-31RA is part of a regulatory program that modulates RNA metabolism, TAP-dependent antigen processing, and regulation of nucleobase metabolism in keratinocytes. Promoter analysis of the module genes indicates that the regulatory program engages IL-31RA through several transcription factors including BARHL1, R3HDM2, FAM119B and IRF1. De novo motif discovery approaches further identified several AT-rich sequences enriched in regions upstream of IL-31RA-correlated genes. The regions are also significantly enriched for microRNA targets including hsa-miR-3163, hsa-miR-4766-5p and hsa-miR-548ar-3p.
These findings contribute to our understanding of the regulation of IL-31RA expression in keratinocytes.

LB057 - Deciphering the regulatory program that modulates interleukin 31 receptor A expression in keratinocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.