title: Interleukin 17A: toward a new understanding of psoriasis pathogenesis.
abstract: Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis.
authors.affiliation: Lynderm Research Inc, Markham, Ontario, Canada. Electronic address: derma@lynderma.com.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Lynde
authors.affiliation: Centre de Recherche Dermatologique du Quebec Metropolitain, Quebec City, Quebec, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Poulin
authors.affiliation: Dermatrials Research Inc, Hamilton, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Vender
authors.affiliation: Durondel CP Inc, Moncton, New Brunswick, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourcier
authors.affiliation: Novartis Pharmaceuticals, Montreal, Quebec, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Khalil
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology*; D018448:Models, Immunological; D011565:Psoriasis / Q000188:drug therapy* / Q000266:history / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; C508717:IL17A protein, human; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha
keywords: T-helper 17 cells; T-helper 1 cells; cytokines; interleukin-17A; interleukin-23; keratinocytes; pathogenesis; psoriasis