IL-27 is expressed in chronic human eczematous skin lesions and stimulates human keratinocytes

BackgroundIL-27 is produced by antigen-presenting cells early during immune responses. IL-27 has been described to support T-cell polarization along the TH1 lineage but also to exert important anti-inflammatory responses in later phases of inflammation in murine models.ObjectiveIt was the aim of this study to analyze the potential role of IL-27 in epidermal inflammatory skin responses in human subjects.MethodsSurface receptor expression and apoptosis of human primary keratinocytes were analyzed by means of flow cytometry. Supernatants of stimulated keratinocytes were either analyzed by means of ELISA or submitted to chemotaxis assays. RT-PCR from lesional skin and phospho-specific Western blotting were performed.ResultsBoth subunits of IL-27 were expressed in chronic lesional allergic eczematous skin, whereas the IL-27 subunit EBV-induced gene 3 was not detectable in the acute phase of eczema. Human primary keratinocytes responded to IL-27. Stimulation of keratinocytes with IL-27 resulted in activation of the signal transducer and activator of transcription 1 and 3 pathways. Major effects found for IL-27 include CXCL10 production and MHC class I upregulation. Importantly, we could demonstrate that IL-27 acts as a priming signal on keratinocytes able to amplify chemokine production and surface molecule expression when used before a second signal, such as TNF-α. The effects of IL-27 could not be mimicked by IL-6, IL-12, or IL-23.ConclusionThese results support the notion that IL-27 might act in an inflammatory, disease-maintaining manner in the epidermal compartment of patients with eczema.