Blubaugh Amanda, Hoover Kathleen, Kim Sujung Jun, Fogle Jonathan E, Sow Fatoumata B, Banovic Frane
College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Boehringer Ingelheim Animal Health, Athens, GA 30601, USA.
Vet Sci. 2024 Mar 1;11(3):109. doi: 10.3390/vetsci11030109.
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, -adjusted value ≤ 0.05). Acute IgE-mediated lesions had a significant upregulation of pro-inflammatory (e.g., , , , , , , ), T helper-(Th)1/IFNγ signal (e.g., , , , , ) and Th2 (e.g., , , , and ) genes, as well as Th2 chemokines (, ). 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.
在犬类中皮内注射抗免疫球蛋白E（IgE）抗体，在大体和组织学上与自然发生的特应性皮炎（AD）相似。然而，激活的炎症和瘙痒途径尚未得到表征。本研究的目的是表征实验性急性犬IgE诱导性病变的炎症转录组，并确定这些转录组与自然发生的人类和犬类急性特应性皮炎转录组的相关性。对8只健康雄性去势比格犬皮内注射抗犬IgE抗体后6小时和24小时采集活检样本；健康皮肤和注射生理盐水的皮肤作为对照。我们从皮肤活检样本中提取总RNA，并使用RNA测序分析转录组。将IgE诱导活检样本的基因表达与同一受试者的对照样本进行比较（变化倍数为1.5，校正值≤0.05）。急性IgE介导的病变中促炎基因（如 、 、 、 、 、 、 ）、辅助性T细胞（Th）1/干扰素γ信号通路相关基因（如 、 、 、 、 ）和Th2相关基因（如 、 、 、 、 ）以及Th2趋化因子（ 、 ）显著上调。通路分析显示JAK-STAT、组胺、白细胞介素-4和白细胞介素-13信号通路强烈显著上调。犬抗犬IgE样本与人类AD样本之间共享差异表达基因（DEG）的斯皮尔曼相关系数显示，抗犬IgE 6小时样本（r = 0.53）和24小时样本（r = 0.47）存在显著的中度正相关。总之，急性犬IgE介导的皮肤病变在健康犬中表现出多极免疫轴上调（Th1、Th2和Th17），类似于急性自发性人类AD病变。
