title: Accumulation and activation of epidermal γδ T cells in a mouse model of chronic dermatitis is not required for the inflammatory phenotype.
abstract: Chronic skin inflammation resulting from a defective epidermal barrier is a hallmark of atopic dermatitis (AD). We previously demonstrated that mice lacking FGF receptors 1 and 2 in keratinocytes (K5-R1/R2 mice) develop an AD-like chronic dermatitis as a result of an impaired epidermal barrier. Here, we show that γδ T cells, which rapidly respond to various insults, accumulate in the epidermis of K5-R1/R2 mice before the development of histological abnormalities. Their number and activation further increase as the phenotype progresses, most likely as a consequence of increased expression of Il-2 and Il-7 and the stress-induced proteins Rae-1, H60c, Mult1, PlexinB2, and Skint1. To determine the role of γδ T cells in the skin phenotype, we generated quadruple mutant K5-R1/-R2 mice lacking γδ T cells. Surprisingly, loss of γδ T cells did not or only marginally affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, and accumulation and activation of different immune cells in the skin of K5-R1/R2 mice, possibly due to partial compensation by αβ T cells. These results demonstrate that γδ T cells do not contribute to the development or maintenance of chronic inflammation in response to a defect in the epidermal barrier.
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Jitka
authors.initials: J
authors.lastname: Sulcova
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Maddaluno
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002908:Chronic Disease; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000276:immunology; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000276:immunology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C527293:H60c protein, mouse; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D007376:Interleukin-2; D015851:Interleukin-7; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C519231:Plxnb2 protein, mouse; C490521:Rae1 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; C529023:Skint1 protein, mouse; C468260:UL16 binding protein 1, mouse; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Atopic dermatitis; Barrier function; Dendritic epidermal T cells; Inflammation; T cells