Oncostatin M Secreted by Skin Infiltrating T Lymphocytes Is a Potent Keratinocyte Activator Involved in Skin Inflammation

• DOI: 10.4049/jimmunol.178.7.4615
• Publication Date: 2014-04-18T22:53:35Z
• Authors: Katia Boniface; Caroline Diveu; Franck Morel; Nathalie Pedretti; Josy Froger; Elisa Ravon; Martine Garcia; Emilie Venereau; Laurence Preisser; Emmanuel Guignouard; Gérard Guillet; Guy Dagregorio; Jérôme Pène; Jean-Pierre Moles; Hans Yssel; Sylvie Chevalier; François-Xavier ...; Hugues Gascan; Jean-Claude Lecron
• Keywords: Keratinocytes; STAT3 Transcription Factor; T-Lymphocytes; Dermatitis; Oncostatin M; [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity; 03 medical and health sciences; Cell Movement; Humans; [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]; [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity; [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]; Cells, Cultured; Oligonucleotide Array Sequence Analysis; Skin; Mitogen-Activated Protein Kinase Kinases; 0303 health sciences; [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology; Immunity, Innate; 3. Good health; [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology; Gene Expression Regulation; [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology; Receptors, Oncostatin M, Type II; [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology

Abstract Cutaneous inflammatory diseases such as psoriasis vulgaris and atopic dermatitis are associated with altered keratinocyte function, as well as with a particular cytokine production profile of skin-infiltrating T lymphocytes. In this study we show that normal human epidermal keratinocytes express a functional type II oncostatin-M (OSM) receptor (OSMR) consisting of the gp130 and OSMRβ components, but not the type I OSMR. The type II OSMR is expressed in skin lesions from both psoriatic patients and those with atopic dermatitis. Its ligand, OSM, induces via the recruitment of the STAT3 and MAP kinase pathways a gene expression profile in primary keratinocytes and in a reconstituted epidermis that is characteristic of proinflammatory and innate immune responses. Moreover, OSM is a potent stimulator of keratinocyte migration in vitro and increases the thickness of a reconstituted epidermis. OSM transcripts are enhanced in both psoriatic and atopic dermatitic skin as compared with healthy skin and mirror the enhanced production of OSM by T cells isolated from diseased lesions. Results from a microarray analysis comparing the gene-modulating effects of OSM with those of 33 different cytokines indicate that OSM is a potent keratinocyte activator similar to TNF-α, IL-1, IL-17, and IL-22 and that it acts in synergy with the latter cytokines in the induction of S100A7 and β-defensin 2 expression, characteristic of psoriatic skin. Taken together, these results demonstrate that OSM and its receptor play an important role in cutaneous inflammatory responses in general and that the specific effects of OSM are associated with distinct inflammatory diseases depending on the cytokine environment.