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Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis

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Item Type:Article
Title:Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis
Creators Name:Augustin, I. and Gross, J. and Baumann, D. and Korn, C. and Kerr, G. and Grigoryan, T. and Mauch, C. and Birchmeier, W. and Boutros, M.
Abstract:Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of gammadelta(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.
Keywords:CD3 Antigens, Cell Proliferation, Chronic Disease, Dendritic Cells, Dermatitis, Epidermis, G-Protein-Coupled Receptors, gamma-delta T-Cell Antigen Receptors, Gene Deletion, Inflammation, Intracellular Signaling Peptides and Proteins, Keratinocytes, Keratins, Lymphocyte Activation, Neutrophil Infiltration, Phenotype, Psoriasis, STAT3 Transcription Factor, T-Lymphocytes, Wnt Proteins, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:1761-1777
Date:26 August 2013
Official Publication:https://doi.org/10.1084/jem.20121871
PubMed:View item in PubMed

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