Oncostatin M Secreted by Skin Infiltrating T Lymphocytes Is a Potent Keratinocyte Activator Involved in Skin Inflammation
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
DOI:
10.4049/jimmunol.178.7.4615
Publication Date:
2014-04-18T22:53:35Z
AUTHORS (19)
ABSTRACT
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.
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CITATIONS (160)
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