title: Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic Skin Inflammation.
abstract: Atopic dermatitis is a chronic inflammatory skin disease characterized by infiltration of eosinophils, T helper cells, and mast cells. The role of mast cells in atopic dermatitis is not completely understood. To define the effects of mast cells on skin biology, we observed that mast cells regulate the homeostatic expression of epidermal differentiation complex and other skin genes. Decreased epidermal differentiation complex gene expression in mice that genetically lack mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein antigens painted on the skin by dendritic cells (DCs) compared with similarly treated wild-type mice, suggesting a protective role for mast cells in exposure to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W-sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT transgenic mice that develop spontaneous atopic dermatitis-like disease that is dependent on T helper cell 2 cytokines and is associated with high serum concentrations of IgE. We observed that Stat6VT × Kit(W-sh/W-sh) mice developed more frequent and more severe allergic skin inflammation than Stat6VT transgenic mice that had mast cells. Together, these studies suggest that mast cells regulate epidermal barrier function and have a potential protective role in the development of atopic dermatitis-like disease.
authors.affiliation: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Sehra
authors.affiliation: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Ana P M
authors.initials: APM
authors.lastname: Serezani
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Ocaña
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
authors.affiliation: Department of Pediatrics and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA. Electronic address: mkaplan2@iupui.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology; D003876:Dermatitis, Atopic / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D004817:Epidermis / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006706:Homeostasis; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation; D053208:Kaplan-Meier Estimate; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000503:physiopathology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D000485:Allergens; D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D007073:Immunoglobulin E