title: Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A.
abstract: Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-17A can turn pathologic and is closely associated with psoriasis. In this study, we generated a novel transgenic mouse model that recapitulates many characteristics of psoriasis. DC-IL-17Aindmice with constitutive low-level expression of IL-17A by CD11c+cells gradually develop skin lesions during adult life. The lesions preferentially occur at sites of mechanical stress and exhibit macroscopic, histologic and genetic hallmarks of psoriatic plaques. Intriguingly, the age of disease onset depends on the levels of IL-17A and disruption of the epidermal barrier by tape-stripping triggers psoriatic plaque formation in the DC-IL-17Aindmodel. In summary, our results suggest that deregulated IL-17A together with epidermal trauma initiates skin inflammation and lesion formation in mice closely resembling plaque-type psoriasis. Due to the gradual development and chronic nature of disease, DC-IL-17Aindmice provide a unique tool to dissect the pathogenesis of human psoriasis and potentially could serve as a model to validate novel therapeutic strategies.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Wohn
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Brand
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: van Ettinger
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Brouwers-Haspels
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 GE Rotterdam, The Netherlands; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. Electronic address: bclausen@uni-mainz.de.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011565:Psoriasis / Q000276:immunology*; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D020381:Interleukin-17
keywords: Epidermal barrier; Interleukin-17; Psoriasis; Skin inflammation; Transgenic mouse model