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

IF 1.9 3区 农林科学 Q3 DERMATOLOGY Veterinary dermatology Pub Date : 2024-10-23 DOI:10.1111/vde.13307
Frane Banovic, Amanda Blubaugh
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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.

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在对屋尘螨(HDM)不敏感的狗身上,由屋尘螨(HDM)引起的表皮皮肤损伤具有 T 辅助细胞 2 炎症和瘙痒生成途径早期激活的特征。
背景:表皮对家养尘螨过敏(HDM-S)的健康狗通常被用作犬特应性皮炎(cAD)模型;然而,HDM-S和HDM-NS诱发AD免疫激活的确切机制仍不清楚:目的:描述 HDM-NS 和 HDM-S 犬在 6 小时和 24 小时内由 HDM 引起的急性表皮皮损的炎症和瘙痒转录组特征;每只犬在 0 小时内未经处理的皮肤作为对照:6只HDM-S和6只HDM-NS实验小猎犬:从Schamber等(G3(Bethesda),2014,4和1787)保存的GEO(GSE58442)中下载并使用R和Bioconductor软件包分析经过处理的表达数据。使用 limma 软件包进行了显著性分析;基因的错误发现率结果:二维主成分分析显示,在 6 小时和 24 小时的时间点上,HDM-NS 和 HDM-S 狗之间没有明显的区分。在 24 小时时间点,HDM 诱导的致敏犬和非致敏犬皮肤病变显示 T 辅助细胞 (Th)2 基因(白细胞介素 [IL]-4R、IL-5、IL-13、CCL13 和 CCL17)以及促炎-(LTB、IL-1A 和 IL-18)、Th1-(CXCL10、OASL 和 MX-1)和 Th17 相关标记物(IL-17B、IL-17F、CCL19 和 CCL20)显著上调。与 Th22 相关的关键标志物 IL-22 仅在 HDM-S 组的 24 小时时间点上调。两组在 24 小时内都有几种非细胞因子瘙痒原的显著上调,如胰蛋白酶、糜蛋白酶、酪蛋白酶 S、periostin 和 neuromedin B:综上所述,我们确定了皮肤外贴HDM贴片会诱导HDM-NS犬体内的免疫变化,其中Th2占主导地位,并激活多种促痒通路。
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来源期刊
Veterinary dermatology
Veterinary dermatology 农林科学-兽医学
CiteScore
3.20
自引率
21.40%
发文量
92
审稿时长
12-24 weeks
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
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