Interleukin 20: discovery, receptor identification, and role in epidermal function.
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.
Blumberg
H
H
Department of Genetics, ZymoGenetics, Inc., 1201 Eastlake Avenue E, Seattle, WA 98102, USA.
Conklin
D
D
Xu
W F
WF
Grossmann
A
A
Brender
T
T
Carollo
S
S
Eagan
M
M
Foster
D
D
Haldeman
B A
BA
Hammond
A
A
Haugen
H
H
Jelinek
L
L
Kelly
J D
JD
Madden
K
K
Maurer
M F
MF
Parrish-Novak
J
J
Prunkard
D
D
Sexson
S
S
Sprecher
C
C
Waggie
K
K
West
J
J
Whitmore
T E
TE
Yao
L
L
Kuechle
M K
MK
Dale
B A
BA
Chandrasekher
Y A
YA
D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004817:Epidermis / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D050796:STAT3 Transcription Factor; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D004268:DNA-Binding Proteins; D007378:Interleukins; D018121:Receptors, Cytokine; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D007633:Keratins; C422042:interleukin 20