title: IL-1RL2 and its ligands contribute to the cytokine network in psoriasis.
abstract: Psoriasis is a common immune-mediated disease in European populations; it is characterized by inflammation and altered epidermal differentiation leading to redness and scaling. T cells are thought to be the main driver, but there is also evidence for an epidermal contribution. In this article, we show that treatment of mouse skin overexpressing the IL-1 family member, IL-1F6, with phorbol ester leads to an inflammatory condition with macroscopic and histological similarities to human psoriasis. Inflammatory cytokines thought to be important in psoriasis, such as TNF-α, IL-17A, and IL-23, are upregulated in the mouse skin. These cytokines are induced by and can induce IL-1F6 and related IL-1 family cytokines. Inhibition of TNF or IL-23 inhibits the increased epidermal thickness, inflammation, and cytokine production. Blockade of IL-1F6 receptor also resolves the inflammatory changes in human psoriatic lesional skin transplanted onto immunodeficient mice. These data suggest a role for IL-1F family members in psoriasis.
authors.affiliation: Amgen, Seattle, WA 98119, USA. halb@novonordisk.com
authors.forename: Hal
authors.initials: H
authors.lastname: Blumberg
authors.forename: Huyen
authors.initials: H
authors.lastname: Dinh
authors.forename: Charles
authors.initials: C
authors.lastname: Dean
authors.forename: Esther S
authors.initials: ES
authors.lastname: Trueblood
authors.forename: Keith
authors.initials: K
authors.lastname: Bailey
authors.forename: Donna
authors.initials: D
authors.lastname: Shows
authors.forename: Narasimharao
authors.initials: N
authors.lastname: Bhagavathula
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Aslam
authors.forename: James
authors.initials: J
authors.lastname: Varani
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Towne
authors.forename: John E
authors.initials: JE
authors.lastname: Sims
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; C508573:Il18r1 protein, mouse; D007375:Interleukin-1; D053727:Interleukin-18 Receptor alpha Subunit; D008024:Ligands; D017472:Receptors, Interleukin-1