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.

Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis.

Cutaneous Lupus Erythematosus (CLE) is a clinically diverse group of autoimmune skin diseases with shared histological features of interface dermatitis and autoantibodies deposited at the dermal-epidermal junction. Various genetic and environmental triggers of CLE promote infiltration of T cells, B cells, neutrophils, antigen presenting cells, and NK cells into lesional skin. In this mini-review, we will discuss the clinical features of CLE, insights into CLE immunopathogenesis, and novel treatment approaches.

Case Series: Gene Expression Analysis in Canine Vogt-Koyanagi-Harada/Uveodermatologic Syndrome and Vitiligo Reveals Conserved Immunopathogenesis Pathways Between Dog and Human Autoimmune Pigmentary Disorders.

Vogt-Koyanagi-Harada syndrome (VKH) and vitiligo are autoimmune diseases that target melanocytes. VKH affects several organs such as the skin, hair follicle, eyes, ears, and meninges, whereas vitiligo is often limited to the skin and mucosa. Many studies have identified immune genes, pathways and cells that drive the pathogeneses of VKH and vitiligo, including interleukins, chemokines, cytotoxic T-cells, and other leukocytes. Here, we present case studies of 2 canines with VKH and 1 with vitiligo, which occurred spontaneously in client-owned companion dogs. We performed comparative transcriptomics and immunohistochemistry studies on lesional skin biopsies from these cases in order to determine if the immunopathogenesis of autoimmune responses against melanocytes are conserved. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CTSW, CXCL10, and CCL5 in both VKH and vitiligo in dogs compared to healthy controls. Similar findings were reported in humans, suggesting that these genes play a role in the pathogenesis of spontaneous VKH and vitiligo. T cell-associated genes, including FOXP3 and TBX21, were enriched, while IGFBP5, FOXO1, and PECAM1 were decreased compared to healthy controls. Further, we identified TGFB3, SFRP2, and CXCL7 as additional potential drivers of autoimmune pigmentary disorders. Future studies exploring the immunopathogenesis of spontaneous autoimmunity will expand our understanding of these disorders, and will be useful in developing targeted therapies, repurposing drugs for veterinary and human medicine, and predicting disease prognosis and treatment response.