title: Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis.
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 γδ(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.
authors.affiliation: Division of Signaling and Functional Genomics and 2 Division of Vascular Oncology and Metastasis, German Cancer Research Center, Heidelberg, Germany. i.augustin@dkfz.de
authors.forename: Iris
authors.initials: I
authors.lastname: Augustin
authors.forename: Julia
authors.initials: J
authors.lastname: Gross
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumann
authors.forename: Claudia
authors.initials: C
authors.lastname: Korn
authors.forename: Grainne
authors.initials: G
authors.lastname: Kerr
authors.forename: Tamara
authors.initials: T
authors.lastname: Grigoryan
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation; D002908:Chronic Disease; D003713:Dendritic Cells / Q000473:pathology; D003872:Dermatitis / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D010641:Phenotype; D011565:Psoriasis / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; C549111:WLS protein, human; D051153:Wnt Proteins; D007633:Keratins
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