title: IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors.
abstract: In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.
authors.affiliation: Unit of Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Savinko
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.forename: Ulpu
authors.initials: U
authors.lastname: Saarialho-Kere
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.forename: Sari
authors.initials: S
authors.lastname: Lehtimäki
authors.forename: Piia
authors.initials: P
authors.lastname: Karisola
authors.forename: Timo
authors.initials: T
authors.lastname: Reunala
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Antti
authors.initials: A
authors.lastname: Lauerma
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D000091344:Filaggrin Proteins; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000485:Allergens; D004768:Enterotoxins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D007166:Immunosuppressive Agents; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D016559:Tacrolimus