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: Jana Zeitvogel, Thomas Werfel, Miriam Wittmann
• Journal: Experimental dermatology (Exp Dermatol) Vol. 21 Issue 6 Pg. 426-30 (Jun 2012) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 22621182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• CXCL10 protein, human
• Chemokine CXCL10
• Interleukin-23
• Interleukins
• Lipopolysaccharides
• MYDGF protein, human
• Interleukin-10
• CD40 Ligand
• Interleukin-12

Topics

• Antigen-Presenting Cells (physiology)
• CD40 Ligand
• Cells, Cultured
• Chemokine CXCL10 (metabolism)
• Humans
• Interleukin-10 (biosynthesis)
• Interleukin-12 (biosynthesis)
• Interleukin-23 (metabolism)
• Interleukins (physiology)
• Lipopolysaccharides
• Macrophages (metabolism)