title: Mast cells are dispensable in a genetic mouse model of chronic dermatitis.
abstract: Chronic inflammatory skin diseases, such as atopic dermatitis, affect a large percentage of the population, but the role of different immune cells in the pathogenesis of these disorders is largely unknown. Recently, we found that mice lacking fibroblast growth factor receptor 1 (Fgfr1) and Fgfr2 (K5-R1/R2 mice) in the epidermis have a severe impairment in the epidermal barrier, which leads to the development of a chronic inflammatory skin disease that shares many features with human atopic dermatitis. Using Fgfr1-/Fgfr2-deficient mice, we analyzed the consequences of the loss of mast cells. Mast cells accumulated and degranulated in the skin of young Fgfr1-/Fgfr2-deficient mice, most likely as a consequence of increased expression of the mast cell chemokine Ccl2. The increase in mast cells occurred before the development of histological abnormalities, indicating a functional role of these cells in the inflammatory skin phenotype. To test this hypothesis, we mated the Fgfr1-/Fgfr2-deficient mice with mast cell-deficient CreMaster mice. Surprisingly, loss of mast cells did not or only mildly affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, accumulation and activation of different immune cells, or expression of different proinflammatory cytokines in the skin. These results reveal that mast cells are dispensable for the development 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: Michael
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Guiducci
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.affiliation: German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland. Electronic address: sabine.werner@biol.ethz.ch.
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D018932:Chemokine CCL2; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2