Characterization of the Pro-Inflammatory and Pruritogenic Transcriptome in Skin Lesions of the Experimental Canine Atopic Acute IgE-Mediated Late Phase Reactions Model and Correlation to Acute Skin Lesions of Human Atopic Dermatitis

Simple Summary Experimental research using atopic dermatitis (AD) models is required to develop and advance novel therapeutics in AD. Intradermal (i.d.) injections of anti-immunoglobulin E (IgE) antibodies in healthy dogs have been utilized as a model of AD; however, the activated inflammatory and pruritic pathways in IgE-induced skin lesions have not been characterized. This study aimed to characterize the inflammatory transcriptome of experimental acute canine IgE-induced lesions using RNA sequencing and to determine how these correlate to the transcriptome of naturally occurring human and canine acute atopic dermatitis. Acute IgE-mediated lesions had a significant upregulation of pro-, T helper-(Th)1 and Th2 genes and Th2 chemokines. Pathway analysis revealed strong significant upregulation of Janus kinase/signal transducers and activators of transcription (JAK-STAT), histamine, IL-4 and IL13 signaling. Correlation analysis to acute human AD lesions showed a significant moderate positive correlation for anti-canine-IgE 6-h samples (r = 0.53) and 24-h samples (r = 0.47). In summary, acute canine IgE-mediated skin lesions exhibit a multipolar immunological axis upregulation (Th1, Th2 and Th17) in healthy dogs, resembling acute spontaneous human AD lesions.Abstract Intradermal injection of anti-immunoglobulin E (IgE) antibodies in dogs grossly and histologically resemble naturally occurring atopic dermatitis (AD). However, the activated inflammatory and pruritic pathways have not been characterized. The objectives of this study were to characterize the inflammatory transcriptome of experimental acute canine IgE-induced lesions and to determine how these correlate to the transcriptome of naturally occurring human and canine acute atopic dermatitis. Biopsies were collected at 6 and 24 h after intradermal injections of anticanine-IgE antibodies to eight healthy male castrated Beagles; healthy and saline-injected skin served as controls. We extracted total RNA from skin biopsies and analyzed transcriptome using RNA-sequencing. Gene expressions of IgE-induced biopsies were compared to that of controls from the same subject (1.5-fold change, p-adjusted value <= 0.05). Acute IgE-mediated lesions had a significant upregulation of pro-inflammatory (e.g., LTB, IL-1B, PTX3, CCL2, IL6, IL8, IL18), T helper-(Th)1/IFN gamma signal (e.g., STAT-1, OASL, MX-1, CXCL10, IL-12A) and Th2 (e.g., IL4R, IL5, IL13, IL33 and POSTN) genes, as well as Th2 chemokines (CCL17, CCL24). Pathway analysis revealed strong significant upregulation of JAK-STAT, histamine, IL-4 and IL13 signaling. Spearman correlation coefficient for the shared DEGs between canine anti-canine-IgE and human AD samples revealed a significant moderate positive correlation for anti-canine-IgE 6-h samples (r = 0.53) and 24-h samples (r = 0.47). In conclusion, acute canine IgE-mediated skin lesions exhibit a multipolar immunological axis upregulation (Th1, Th2 and Th17) in healthy dogs, resembling acute spontaneous human AD lesions.