title: Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice.
abstract: Atopic dermatitis (AD) is a common inflammatory skin disease of unknown etiology. Cutaneous infection with microbes such as Staphylococcus aureus and/or skin cleansing with detergent exacerbates clinical AD. Here, we generated an AD animal model by destroying skin barrier function with detergent and subsequent topical application of protein A from S. aureus (SpA). NC/Nga mice, which genetically have reduced skin barrier function, and BALB/c mice having intact skin barrier function, were susceptible to this combination and developed severe and moderate AD, respectively, associated with dermal accumulation of eosinophils and mast cells. Both types of mice showed an increase in serum levels of IL-18, but not IgE. The epidermis of the NC/Nga mice rapidly expressed T helper type 1 (Th1)-associated chemokines, including ligands for CXCR3 and CCR5, after application of both SpA and detergent, but not after application of detergent alone. Although treatment with detergent induced moderate Th1 cell response, additional SpA treatment was a prerequisite for induction of the differentiation of naive T cells toward unique Th1 cells, termed "super Th1 cells," capable of producing both Th1 (IFN-gamma) and T helper type 2 cytokine (IL-13), as well as IL-3, and expressing CXCR3 and CCR5. Induction of super Th1 cells required IL-18 stimulation. Blockade of IL-18 prevented AD development, whereas blockade of IL-3 partially prevented AD development, suggesting a contribution of IL-18-dependent IL-3 production to AD with cutaneous mastocytosis. il18-/-BALB/c mice similarly evaded SDS/SpA-induced AD. Thus, IL-18 might be important for the development of infection-associated AD by induction of IL-3 from super Th1 cells.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Terada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Imai
authors.forename: Koubun
authors.initials: K
authors.lastname: Yasuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsui
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002454:Cell Differentiation; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology*; D007377:Interleukin-3 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008407:Mast Cells / Q000166:cytology; D034701:Mastocytosis, Cutaneous / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology
chemical_list: D001426:Bacterial Proteins; D018793:Interleukin-13; D020382:Interleukin-18; D007377:Interleukin-3; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma