title: IL-27 acts as a priming signal for IL-23 but not IL-12 production on human antigen-presenting cells.
abstract: IL-27 belongs to the IL-12 family of cytokines and has been described not only to support T-cell polarization along the Th1 lineage, but also to induce important anti-inflammatory responses in later phases of inflammation. We and others have previously shown that the cytokine IL-27 has an important impact on the chronic manifestation of inflammatory skin diseases. Thus, the aim of this study was to specify the effects of IL-27 on the human antigen-presenting cell (APC) subtype inflammatory dendritic epidermal cells (IDEC), which are known to play an important role in eczema. IDEC and blood-derived human macrophages were generated from human peripheral blood and stimulated with IL-27. Functional responses of the cells were analysed by intracellular cytokine staining, ELISA and FlowCytomix. IL-27 was found to be the only IL-12 family member that acts on human APC as a priming signal for IL-23 but not IL-12 production. We confirmed for macrophages that IL-27 limits lipopolysaccharide-induced IL-10 production and detected the same tendency for IDEC. Furthermore, we showed that this also applies to CD40L-induced IL-10 expression in both investigated human APC subsets. We demonstrate that IL-27 exerts pro-inflammatory effects on human APC in particular in the context of a range of bacterial-derived TLR ligands. Hence, our study builds upon the idea that IL-27 exerts a pro-inflammatory effect on innate immune and tissue-resident cells and may drive eczematous reaction - in particular in the context of bacterial superinfection - towards a chronic phase.
authors.affiliation: Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany. zeitvogel.jana@mh-hannover.de
authors.forename: Jana
authors.initials: J
authors.lastname: Zeitvogel
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Miriam
authors.initials: M
authors.lastname: Wittmann
mesh_terms: D000938:Antigen-Presenting Cells / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000378:metabolism*; D007378:Interleukins / Q000502:physiology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D053759:Interleukin-23; D007378:Interleukins; D008070:Lipopolysaccharides; C464565:MYDGF protein, human; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12