Shared inflammatory and skin-specific gene signatures reveal common drivers of discoid lupus erythematosus in canines, humans and mice

• Published in: Current research in immunology 2021, Vol.2, p.41-51
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Canine (dog); Chemokine; Comparative immunology; Cutaneous lupus erythematosus; Cytokine; Discoid lupus; Immunopathogenesis; Research Paper; Skin
• ISSN: 2590-2555; 2590-2555
• DOI: 10.1016/j.crimmu.2021.03.003

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 CXCL10, ISG15, and an S100 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. [Display omitted] •Canine DLE lesions express known drivers of pathogenesis including CXCL10, IFNG, FAS.•Enrichment of key cell types, including T, B, NK cells, is observed in canine DLE.•Canine, mouse and human DLE share similar proinflammatory profiles.•Canine DLE exhibits downregulated skin homeostatic and immune regulatory genes.