title: Psoriasis: dysregulation of innate immunity.
abstract: The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O.Box 22700, 1100 DE Amsterdam, the Netherlands. j.d.bos@amc.uva.nl
authors.forename: J D
authors.initials: JD
authors.lastname: Bos
authors.forename: M A
authors.initials: MA
authors.lastname: de Rie
authors.forename: M B M
authors.initials: MB
authors.lastname: Teunissen
authors.forename: G
authors.initials: G
authors.lastname: Piskin
mesh_terms: D000941:Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D015603:Keratinocytes / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D018448:Models, Immunological; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D014409:Tumor Necrosis Factor-alpha