title: Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. Although IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we show that IL-17E(+) cells are more abundant than IL-17A(+) cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E(+) cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather take up IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a proinflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Luisa
authors.initials: L
authors.lastname: Senra
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Romaine
authors.initials: R
authors.lastname: Stalder
authors.affiliation: Division of Dermatology and Venereology, Geneva University Hospitals and School of Medicine, Geneva, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Alvarez Martinez
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Immunology and Allergy, Geneva University Hospitals and School of Medicine, Geneva, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Chizzolini
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Dermatology and Venereology, Geneva University Hospitals and School of Medicine, Geneva, Switzerland. Electronic address: wolf-henning.boehncke@hcuge.ch.
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Nicolò Costantino
authors.initials: NC
authors.lastname: Brembilla
mesh_terms: D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D002966:Clathrin; D016207:Cytokines; D020381:Interleukin-17