title: Mast cells are required for full expression of allergen/SEB-induced skin inflammation.
abstract: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ(-/-) or Rag1(-/-)). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcɛRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Siavash
authors.initials: S
authors.lastname: Namiranian
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Haley
authors.initials: H
authors.lastname: Glatthorn
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Dolan
authors.affiliation: Division of Pulmonary Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Departments of Pathology and of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA. Electronic address: toshi@liai.org.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Jamora
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA; Laboratory of Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation; D003872:Dermatitis / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000503:physiopathology; D004485:Eczema / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology; D050356:Lipid Metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D039981:Pyroglyphidae; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000485:Allergens; D004768:Enterotoxins; D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal