IL-27 is expressed in chronic human eczematous skin lesions and stimulates human keratinocytes.
BACKGROUND
IL-27 is produced by antigen-presenting cells early during immune responses. IL-27 has been described to support T-cell polarization along the T(H)1 lineage but also to exert important anti-inflammatory responses in later phases of inflammation in murine models.


OBJECTIVE
It was the aim of this study to analyze the potential role of IL-27 in epidermal inflammatory skin responses in human subjects.


METHODS
Surface 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.


RESULTS
Both 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-alpha. The effects of IL-27 could not be mimicked by IL-6, IL-12, or IL-23.


CONCLUSIONS
These results support the notion that IL-27 might act in an inflammatory, disease-maintaining manner in the epidermal compartment of patients with eczema.
Wittmann
Miriam
M
Department of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany. M.Wittmann@leeds.ac.uk
Zeitvogel
Jana
J
Wang
Dong
D
Werfel
Thomas
T
D015153:Blotting, Western; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D004485:Eczema / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects*; D018123:Receptors, Interleukin / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D054357:Chemokine CXCL10; C112441:IL27RA protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D007378:Interleukins; C464565:MYDGF protein, human; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D018799:Intercellular Adhesion Molecule-1