Construction of a chronic spontaneous urticaria-like mouse model based on passive cutaneous anaphylaxis and its transcriptome analysis

Background: Chronic spontaneous urticaria(CSU) is a common immune-related skin disorder with an unclear pathogenesis and no universally accepted animal model. In this study, we compared the commonly used passive cutaneous anaphylaxis(PCA) model with an animal model featuring 2,4-Dinitrophenyl-human serum albumin(DNP-HSA) specific IgE and repeated DNP-HSA stimulation. We performed skin transcriptome analysis and compared the results with publicly available human CSU skin transcriptome data to investigate the representativeness of the improved recurrent passive cutaneous anaphylaxis(Re-PCA) model for CSU.Methods: We established a Re-PCA model via six repeated injections of DNP-HSA-specific IgE and DNP-HSA, comparing it with the PCA model. We assessed vascular permeability, scratch frequency scoring, histological staining, flow cytometry, reverse transcription PCR, ELISA, and RNA-seq to compare phenotypic differences. The RNA-seq gene expression profiles were then compared with human CSU skin RNA-seq data from the GEO database.Results: We found that the Re-PCA model exhibited stable chronic urticaria-like skin changes. Lesional tissues showed significantly increased degranulated mast cells and demonstrated tissue infiltration including neutrophils, dendritic cells, Th1, Th2, and Th17 cells. Concurrently, peripheral blood histamine levels were significantly elevated in mice, and the gene expression profile of the lesions revealed enrichment of multiple genes and signaling pathways associated with CSU. This study provides a novel animal model of CSU and compares it with the established PCA model.Conclusions: We established an animal model of CSU induced by repeated IgE/ DNP-HSA activation of mast cells. This model facilitates research into the pathogenesis of CSU and advances our understanding of its underlying mechanisms.