title: IL-23-mediated epidermal hyperplasia is dependent on IL-6.
abstract: Psoriasis is a chronic inflammatory skin disease primarily driven by Th17 cells. IL-23 facilitates the differentiation and induces complete maturation of Th17 cells. Lesional psoriatic skin has increased levels of IL-23 and recent studies show that intradermal injections of IL-23 induce a psoriasis-like skin phenotype in mice. We have now characterized the IL-23-induced skin inflammation in mice at the molecular level and found a significant correlation with the gene expression profile from lesional psoriatic skin. As observed in psoriasis, the pathogenesis of the IL-23-induced skin inflammation in mice is driven by Th17 cells. We demonstrate a dramatic upregulation of IL-6 mRNA and protein after intradermal injections of IL-23 in mice. Using IL-6(-/-) mice we show that IL-6 is essential for development of the IL-23-elicited responses. Despite producing high levels of IL-22, IL-6(-/-) mice were unable to express the high-affinity IL-22 receptor chain and produced minimal IL-17A in response to intradermal injections of IL-23. In conclusion, we provide evidence for the critical role played by IL-6 in IL-23-induced skin inflammation and show that IL-6 is required for expression of IL-22R1A.
authors.affiliation: Department of Pharmacology, LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Josefine
authors.initials: J
authors.lastname: Lindroos
authors.forename: Lars
authors.initials: L
authors.lastname: Svensson
authors.forename: Hanne
authors.initials: H
authors.lastname: Norsgaard
authors.forename: Paola
authors.initials: P
authors.lastname: Lovato
authors.forename: Kristian
authors.initials: K
authors.lastname: Moller
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hagedorn
authors.forename: Gunnar Marius
authors.initials: GM
authors.lastname: Olsen
authors.forename: Tord
authors.initials: T
authors.lastname: Labuda
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018123:Receptors, Interleukin / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor