title: The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses.
abstract: Psoriasis is a complex inflammatory process resulting from activation of the well-defined interleukin (IL)-23/T17 cytokine axis. We review the role of key cytokines IL-17 and IL-23 in psoriasis, as well as tumor necrosis factor (TNF)α, focusing on therapeutic cytokine interventions and what they reveal about psoriatic inflammation. The potential role of recently described epidermal IL-36RN and CARD14 genetic mutations in psoriasis pathogenesis is also explored, because they augment keratinocyte responses to proinflammatory cytokines. The discovery of these genetic mutations in familial and pustular psoriasis suggests new links between cytokine-induced gene products and IL-1 family members from keratinocytes, which may regulate features of the disease, including epidermal hyperplasia and neutrophil infiltrating responses.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Chris B
authors.initials: CB
authors.lastname: Russell
authors.forename: David A
authors.initials: DA
authors.lastname: Martin
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Towne
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D004817:Epidermis / Q000473:pathology; D059647:Gene-Environment Interaction; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011565:Psoriasis / Q000235:genetics / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D008565:Membrane Proteins; D018123:Receptors, Interleukin; C571244:interleukin-36 receptor, human; C426243:CARD14 protein, human; D006162:Guanylate Cyclase