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Juan Narvaez

Juan Narvaez

The University of Georgia
College of Veterinary Medicine
Class of 2019

Research Interests

Multi-parameter analysis of skin lesions in MRL/lpr mice model of chronic cutaneous lupus erythematosus

Juan C. Narvaez, Amanda Blubaugh, Robert Gogal Jr, Kathleen Hoover, Keith Linder and Frane Banovic

Department of Small Animal Medicine and Surgery (Narvaez, Blubaugh, Hoover, Banovic), and Department of Veterinary Biosciences and Diagnostic Imaging (Gogal), College of Veterinary Medicine, University of Georgia, Athens, GA; Department of Population Health and Pathobiology (Linder), North Carolina State University, Raleigh, NC

Chronic cutaneous lupus erythematosus (CCLE) is a photosensitive autoimmune disease characterized by a strong type I interferon-associated inflammation. The lupus mouse model MRL/lpr is the most intensively studied CCLE model, however, global patterns of gene expression and inflammatory pathways leading to local skin damage are unknown. The objectives of this study were to characterize chronic skin lesional transcriptome of 10 MRL/lpr mice; lesional and non-lesional skin biopsies were obtained 3 to 8 weeks after the onset. We extracted mRNA from skin biopsies and the transcriptome was assessed using RNA-seq. Gene expression of lesional skin was compared to that of non-lesional skin specimens (1.5-fold change, 0.05 adjusted P-values). Histopathological findings revealed a mild lymphocyte-rich interface dermatitis and folliculitis with zones of basal keratinocytes vacuolation. Comparing the lesional mRNA expression to non-lesional skin, we identified a large set of 3,042 genes significantly up-regulated. The Th1 signal (STAT1, OASL, MX1, IFNg) and T-cell trafficking chemokine, CXCL10, were among the upregulated genes. The differentially expressed genes (DEGs) within the MRL/lpr lesional pathology signature reflect an activated immune and inflammatory system and belong to dysregulated KEGG pathways such as Jak/Stat signaling pathway, T-cell receptor-, chemokine-cell receptor-signaling pathway and cytokine-cytokine receptor interaction. Functional annotation with human CCLE revealed mechanistic pathway and processes commonality (type I interferon pathways, apoptotic/survival pathways). In conclusion, the MRL/lpr skin lesions show robust immune and inflammatory responses that resemble human CCLE transcriptome results.

Research Grant: Self-funded

Student Support: Boehringer Ingelheim Veterinary Scholars Program

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