title: Dendritic cells activated by IFN-γ/STAT1 express IL-31 receptor and release proinflammatory mediators upon IL-31 treatment.
abstract: IL-31 is a T cell-derived cytokine that signals via a heterodimeric receptor composed of IL-31Rα and oncostatin M receptor β. Although several studies have aimed to investigate IL-31-mediated effects, the biological functions of this cytokine are currently not well understood. IL-31 expression correlates with the expression of IL-4 and IL-13 and is associated with atopic dermatitis in humans, indicating that IL-31 is involved in Th2-mediated skin inflammation. Because dendritic cells are the main activators of Th cell responses, we posed the question of whether dendritic cells express the IL-31R complex and govern immune responses triggered by IL-31. In the current study, we report that primary human CD1c(+) as well as monocyte-derived dendritic cells significantly upregulate the IL-31Rα receptor chain upon stimulation with IFN-γ. EMSAs, chromatin immunoprecipitation assays, and small interfering RNA-based silencing assays revealed that STAT1 is the main transcription factor involved in IFN-γ-dependent IL-31Rα expression. Subsequent IL-31 stimulation resulted in a dose-dependent release of proinflammatory mediators, including TNF-α, IL-6, CXCL8, CCL2, CCL5, and CCL22. Because these cytokines are crucially involved in skin inflammation, we hypothesize that IL-31-specific activation of dendritic cells may be part of a positive feedback loop driving the progression of inflammatory skin diseases.
authors.affiliation: Department of Molecular Biology, University of Salzburg, A-5020 Salzburg, Austria. jutta.horejs_hoeck@sbg.ac.at
authors.forename: Jutta
authors.initials: J
authors.lastname: Horejs-Hoeck
authors.forename: Harald
authors.initials: H
authors.lastname: Schwarz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lamprecht
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maier
authors.forename: Stefan
authors.initials: S
authors.lastname: Hainzl
authors.forename: Maria
authors.initials: M
authors.lastname: Schmittner
authors.forename: Gernot
authors.initials: G
authors.lastname: Posselt
authors.forename: Angelika
authors.initials: A
authors.lastname: Stoecklinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Hawranek
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005246:Feedback; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000502:physiology*; D012871:Skin Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C502188:IL31RA protein, human; D018836:Inflammation Mediators; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma