title: IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis.
abstract: Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.
authors.affiliation: Discovery Research, Schering-Plough Biopharma (formerly DNAX Research, Inc.), Palo Alto, CA 94304, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Chan
authors.forename: Wendy
authors.initials: W
authors.lastname: Blumenschein
authors.forename: Erin
authors.initials: E
authors.lastname: Murphy
authors.forename: Caroline
authors.initials: C
authors.lastname: Diveu
authors.forename: Maria
authors.initials: M
authors.lastname: Wiekowski
authors.forename: Susan
authors.initials: S
authors.lastname: Abbondanzo
authors.forename: Linda
authors.initials: L
authors.lastname: Lucian
authors.forename: Richard
authors.initials: R
authors.lastname: Geissler
authors.forename: Scott
authors.initials: S
authors.lastname: Brodie
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Kimball
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Gorman
authors.forename: Kathleen
authors.initials: K
authors.lastname: Smith
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kastelein
authors.forename: Terrill K
authors.initials: TK
authors.lastname: McClanahan
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
mesh_terms: D000818:Animals; D004817:Epidermis / Q000254:growth & development / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D053759:Interleukin-23 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D053759:Interleukin-23; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; C492510:interleukin-20 receptor