title: Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice.
abstract: Transgenic mice expressing the mouse interleukin 33 (IL-33) gene driven by a keratin 14 promoter were generated. The skin-selective expression of the IL-33 gene was enhanced, and intense immunofluorescence for IL-33 was evident in the nuclei of the epidermis. Spontaneous itchy dermatitis developed in those mice at 6-8 wk of age in specific pathogen-free conditions. In the lesional skin, the epidermis was thickened and the eosinophils were infiltrated with increased expression of the eosinophil peroxidase and major basic protein genes. Mast cells were also abundant there, and blood histamine and total IgE levels were high. Those phenotypes closely resemble the features of atopic dermatitis. In peripheral blood and lesional skin, IL-5, IL-13, regulated upon activation, normally T-expressed, and presumably secreted (RANTES)/CCL5, and Eotaxin 1/CCL11 were increased, whereas TNF-α, IFN-γ, and thymic stromal lymphopoietin (TSLP) were unaltered. Furthermore, the proportion of group 2 innate lymphoid cells (ILC2s), which produce IL-5, were significantly increased in the lesional skin, peripheral blood, and regional lymph nodes. The dermatitis with eosinophil infiltration was improved by the administration of an anti-IL-5 antibody. These results suggest that the expression of IL-33 in the skin activates an immune response involving ILC2 and that this process might play a crucial role in the pathogenesis of allergic inflammation that is characteristic of atopic dermatitis.
authors.affiliation: Departments of Dermatology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Imai
authors.forename: Koubun
authors.initials: K
authors.lastname: Yasuda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Haneda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamanishi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003876:Dermatitis, Atopic / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006632:Histamine / Q000097:blood; D007113:Immunity, Innate / Q000276:immunology*; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
chemical_list: D016207:Cytokines; D017931:DNA Primers; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D006632:Histamine
keywords: Atopy; natural helper cells; nuocytes
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