Epicutaneous house dust mite (HDM)-induced skin lesions feature early activation of T helper 2 inflammatory and pruritogenic pathways in HDM-nonsensitised dogs.
{"title":"Epicutaneous house dust mite (HDM)-induced skin lesions feature early activation of T helper 2 inflammatory and pruritogenic pathways in HDM-nonsensitised dogs.","authors":"Frane Banovic, Amanda Blubaugh","doi":"10.1111/vde.13307","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To characterise the inflammatory and pruritogenic transcriptome of acute epicutaneous HDM-induced skin lesions at 6 h and 24 h in HDM-NS and HDM-S dogs; untreated skin at 0 h from each dog served as control.</p><p><strong>Animals: </strong>Six HDM-S and six HDM-NS laboratory beagles.</p><p><strong>Materials and methods: </strong>Processed expression data from GEO deposited by Schamber et 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 <0.05 and fold-change ≤/≥1.5 were considered significantly differentially expressed (DEGs).</p><p><strong>Results: </strong>A 2D principal component analysis revealed no clear separation between HDM-NS and HDM-S dogs at 6 h and 24 h time points. HDM-induced skin lesions in sensitised and nonsensitised dogs at the 24 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 h time point. Both groups at 24 h featured significant upregulation of several noncytokine pruritogens, such as trypsin, chymase, cathepsin S, periostin and neuromedin B.</p><p><strong>Conclusions and clinical relevance: </strong>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.</p>","PeriodicalId":23599,"journal":{"name":"Veterinary dermatology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary dermatology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/vde.13307","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
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 h and 24 h in HDM-NS and HDM-S dogs; untreated skin at 0 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 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 <0.05 and fold-change ≤/≥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 h and 24 h time points. HDM-induced skin lesions in sensitised and nonsensitised dogs at the 24 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 h time point. Both groups at 24 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.
期刊介绍:
Veterinary Dermatology is a bi-monthly, peer-reviewed, international journal which publishes papers on all aspects of the skin of mammals, birds, reptiles, amphibians and fish. Scientific research papers, clinical case reports and reviews covering the following aspects of dermatology will be considered for publication:
-Skin structure (anatomy, histology, ultrastructure)
-Skin function (physiology, biochemistry, pharmacology, immunology, genetics)
-Skin microbiology and parasitology
-Dermatopathology
-Pathogenesis, diagnosis and treatment of skin diseases
-New disease entities