Abstract
A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.
MeSH terms
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Animals
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Cell Line
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Chromosome Mapping
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Cloning, Molecular
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DNA-Binding Proteins / metabolism
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Dimerization
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Epidermis / chemistry
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Epidermis / immunology*
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Epidermis / pathology
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Gene Expression / immunology
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Humans
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukins / chemistry
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Interleukins / genetics*
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Interleukins / immunology
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Keratinocytes / cytology
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Keratinocytes / immunology
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Keratins / genetics
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Psoriasis / immunology
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Psoriasis / pathology
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Receptors, Cytokine / chemistry
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Receptors, Cytokine / genetics*
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Receptors, Cytokine / immunology*
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STAT3 Transcription Factor
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Sequence Homology, Amino Acid
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Trans-Activators / metabolism
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Up-Regulation / immunology
Substances
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DNA-Binding Proteins
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Interleukins
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Receptors, Cytokine
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Interleukin-10
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Keratins
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interleukin 20
Associated data
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GENBANK/AF184971
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GENBANK/AF192498
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GENBANK/AF224266
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GENBANK/AF224267
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GENBANK/X24379