Garelli Colton J, Wong Neil B, Piedra-Mora Cesar, Wrijil Linda M, Scarglia Gina, David Clement N, Almela Ramón M, Robinson Nicholas A, Richmond Jillian M
Dermatology Department, University of Massachusetts Medical School, Worcester, MA, USA.
Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton MA, USA.
Curr Res Immunol. 2021 Mar 31;2:41-51. doi: 10.1016/j.crimmu.2021.03.003. eCollection 2021.
Autoimmune skin diseases are complex and are thought to arise from a combination of genetics and environmental exposures, which trigger an ongoing immune response against self-antigens. Companion animals including cats and dogs are known to develop inflammatory skin conditions similar to humans and share the same environment, providing opportunities to study spontaneous disease that encompasses genetic and environmental factors with a One Health approach. A strength of comparative immunology approaches is that immune profiles may be assessed across different species to better identify shared or conserved pathways that might drive inflammation. Here, we performed a comparative study of skin from canine discoid lupus erythematosus (DLE) using NanoString nCounter technology. We compared these gene expression patterns to those of human DLE and a mouse model of cutaneous lupus. We found strong interferon signatures, with , and an gene family member among the highest, most significant DEGs upregulated across species. Cell type analysis revealed marked T-cell and B-cell infiltration. Interestingly, canine DLE samples also recapitulated downregulated skin homeostatic genes observed in human DLE. We conclude that spontaneous DLE in dogs captures many features that are present in human disease and may serve as a more complete model for conducting further genomic and/or transcriptomic studies.
自身免疫性皮肤病很复杂，被认为是由遗传因素和环境暴露共同作用引起的，这些因素会引发针对自身抗原的持续免疫反应。已知包括猫和狗在内的伴侣动物会出现与人类相似的炎症性皮肤病，并且共享相同的环境，这为采用“同一健康”方法研究包含遗传和环境因素的自发性疾病提供了机会。比较免疫学方法的一个优势在于，可以跨不同物种评估免疫谱，以更好地识别可能驱动炎症的共享或保守途径。在此，我们使用NanoString nCounter技术对犬盘状红斑狼疮（DLE）的皮肤进行了一项比较研究。我们将这些基因表达模式与人类DLE和皮肤狼疮小鼠模型的基因表达模式进行了比较。我们发现了强烈的干扰素特征，在跨物种上调的最高、最显著的差异表达基因（DEG）中，有 ，以及一个 基因家族成员。细胞类型分析显示有明显的T细胞和B细胞浸润。有趣的是，犬DLE样本也重现了在人类DLE中观察到的皮肤稳态基因下调的情况。我们得出结论，犬自发性DLE具有许多人类疾病中存在的特征，可作为进行进一步基因组和/或转录组研究的更完整模型。
