title: IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction?
abstract: Atopic dermatitis (AD) is a common skin disease associated with a T(H)2 response and increased levels of T(H)2-associated cytokines and IgE. The mechanisms resulting in skewing the immune response in a T(H)2 direction in AD are not fully elucidated. However, such skewing has recently been associated with IL-25 in a murine model for allergic airway disease. The aim of this study was to investigate whether IL-25 may have a role in AD. We have identified IL-25-producing cells within the dermis of AD patients and propose that these cells are dendritic cells (DCs). This is supported by in vitro experiments that indicate that monocyte-derived DCs are capable of producing IL-25. As null mutations of filaggrin are associated with the development of an impaired skin barrier in AD, we investigated whether IL-25 affects filaggrin synthesis by keratinocytes. Using mRNA analysis, we have shown that IL-25 stimulation does indeed decrease filaggrin synthesis in cultured keratinocytes. These results suggest that IL-25 produced by DCs could have a dual role as both an inducer of the T(H)2 response and as an inhibitor of filaggrin synthesis, thereby directly affecting skin barrier function in AD patients.
authors.affiliation: Institute of Medical Microbiology and Immunology, Aarhus University, Aarhus C, Denmark. malenel@microbiology.au.dk
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.forename: Christian
authors.initials: C
authors.lastname: Vestergaard
authors.forename: Kaare
authors.initials: K
authors.lastname: Kemp
authors.forename: Gitte B
authors.initials: GB
authors.lastname: Christensen
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.forename: Mette
authors.initials: M
authors.lastname: Deleuran
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D000091344:Filaggrin Proteins; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens; C486701:IL25 protein, human; D020381:Interleukin-17; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D053722:Receptors, Interleukin-17