In chronic inflammatory skin diseases (CISD), different transcription factors have emerged as crucial players in the pathogenesis. The CCAAT/enhancer-binding protein beta (CEBPB) is a well-known transcription factor sensitive to various immunogenic stimuli. In this study, we investigate CEBPB in Keratinocytes and aim at dissecting its functional role in skin inflammation. Using a computational approach combining transcriptomics with deep clinical phenotyping of CISD patients, we identified CEBPB as novel factor associated with skin inflammation. In spatial transcriptomics, bulk RNASeq and Immunohistochemistry, CEBPB was significantly upregulated in the lesional skin of Lichen Planus, Atopic Dermatitis and Psoriasis (Pso) patients, with the highest levels in Pso. Similarly, in vitro stimulated human Keratinocytes showed the strongest CEBPB induction with Pso-relevant cytokines. RNASeq of CEBPB knockout (KO) Keratinocytes revealed regulation of various disease-relevant pathways. Using a 3D Psoriatic skin model, we show that CEBPB KO inhibited acanthosis development, Keratinocytes proliferation and mitochondrial metabolism. Moreover, it reduced secretion of neutrophil attracting chemokines. In line, CEBPB levels positively correlated with clinical scores of acanthosis and neutrophil infiltration. Finally, the CEBPB gene signature could be traced back in patients showing a positive enrichment in Psoriasis. In summary, we show that CEBPB is a novel regulatory node in skin inflammation and a control point for the pathogenic epithelial response in Psoriasis. Our findings hence hold substantial promise for the use of CEBPB as a new therapeutic target in skin inflammation.

ESDR328 - The transcription factor CEBPB is a novel hub gene and multi-functional disease driver in Psoriatic skin inflammation

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.