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

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.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JMR is an inventor on patent application #15/851,651, “Anti-human CXCR3 antibodies for the Treatment of Vitiligo” which covers targeting CXCR3 for the treatment of vitiligo; and on patent #62489191, “Diagnosis and Treatment of Vitiligo” which covers targeting IL-15 and Trm for the treatment of vitiligo. NAR and GS are employees of bluebird bio. CND is an employee of NanoString Technologies.
(© 2021 The Author(s).)