Comparison of transcriptomic profiles in edge to center of plaque reveals chronological molecular events in psoriatic plaque formation

Background: Peripheral edge (PE) of plaques contains inflammatory molecules and has potential to initiate plaque formation, while the center (CE) of plaques has regression trends.Objective: To elucidate the chronological molecular events by comparing the gene profiles in PE skin to those in CE skin.Methods: Biopsied PE, CE, and uninvolved (UN) skin samples were analyzed by next-generation sequencing. Three groups of differentially expressed genes (DEGs) were analyzed, PE/UN-, CE/UN-, and PE/CE-skin-derived DEGs.Results: PE skin contained inflammation-priming molecules, such as S100A7 and S100A15, and in-flammatory drivers, such as interleukin (IL)-36 alpha. IL-6 signaling was more active in PE than in CE skin. IL-8, S100A7, S100A8, S100A9, and human beta-defensin-2 were all regulated with the similar pattern in both areas. However, PE skin created a more active inflammatory network and downstream functions, including che-motaxis and angiogenesis, were more prominent than in CE skin. Conversely, CE skin, where epidermal growth factor and hepatocyte growth factor increased their activity, was found to be more stable.Conclusion: This is the first RNA-seq-based report to determine the chronological molecular events in plaque formation. In the early phase, inflammation might be initiated through molecules, such as IL-36 alpha, S100A7, and S100A15, as observed in PE skin. The inflammation state in PE skin progresses to the more stable state found in CE skin. In CE skin, the growth factor activities are increased, which might lead to attenuation of initial inflammation and initiation of the regression phase. These molecular events may accelerate research towards developing novel therapies for psoriasis.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.