Epicutaneous house dust mite (HDM)-induced skin lesions feature early activation of T helper 2 inflammatory and pruritogenic pathways in HDM-nonsensitised dogs.

Abstract

BACKGROUND: Epicutaneously house dust mite-sensitised (HDM-S) healthy dogs are commonly used as canine atopic dermatitis (cAD) models; however, the exact mechanisms of HDM-induced AD immune activation in HDM-S and HDM-nonsensitised (NS) dogs remain unclear. OBJECTIVES: To characterise the inflammatory and pruritogenic transcriptome of acute epicutaneous HDM-induced skin lesions at 6&#x2009;h and 24&#x2009;h in HDM-NS and HDM-S dogs; untreated skin at 0&#x2009;h from each dog served as control. ANIMALS: Six HDM-S and six HDM-NS laboratory beagles. MATERIALS AND METHODS: Processed expression data from GEO deposited by Schamber et&#xa0;al. (G3 (Bethesda), 2014, 4 and 1787) (GSE58442) were downloaded and analysed using R and the Bioconductor package. Significance analysis was performed with the limma package; genes with false discovery rate&#x2009;<0.05 and fold-change &#x2264;/&#x2265;1.5 were considered significantly differentially expressed (DEGs). RESULTS: A 2D principal component analysis revealed no clear separation between HDM-NS and HDM-S dogs at 6&#x2009;h and 24&#x2009;h time points. HDM-induced skin lesions in sensitised and nonsensitised dogs at the 24&#x2009;h time point showed significant upregulation of T helper cell (Th)2 genes (interleukin [IL]-4R, IL-5, IL-13, CCL13 and CCL17), as well as proinflammatory- (LTB, IL-1A and IL-18), Th1- (CXCL10, OASL and MX-1) and Th17-related markers (IL-17B, IL-17F, CCL19 and CCL20). The key Th22-related maker, IL-22, was upregulated only in the HDM-S group at the 24&#x2009;h time point. Both groups at 24&#x2009;h featured significant upregulation of several noncytokine pruritogens, such as trypsin, chymase, cathepsin S, periostin and neuromedin B. CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, we establish that epicutaneous HDM patch application induces immune changes in HDM-NS dogs with Th2 dominance and activates several itch-promoting pathways.