Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2.
The receptor for IL-26 (AK155), a cytokine of the IL-10 family, has not previously been defined. We demonstrate that the active receptor complex for IL-26 is a heterodimer composed of two receptor proteins: IL-20R1 and IL-10R2. Signaling through the IL-26R results in activation of STAT1 and STAT3 which can be blocked by neutralizing Abs against IL-20R1 or IL-10R2. IL-10R2 is broadly expressed on a wide variety of tissues, whereas only a limited number of tissues express IL-20R1. Therefore, the ability to respond to IL-26 is restricted by the expression of IL-20R1. IL-10, IL-19, IL-20, IL-22, and IL-24 fail to signal through the combination of IL-10R2 and IL-20R1 proteins, demonstrating that this receptor combination is unique and specific for IL-26.
Sheikh
Faruk
F
Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Baurin
Vitaliy V
VV
Lewis-Antes
Anita
A
Shah
Nital K
NK
Smirnov
Sergey V
SV
Anantha
Shubha
S
Dickensheets
Harold
H
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Zdanov
Alexander
A
Donnelly
Raymond P
RP
Kotenko
Sergei V
SV
D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D019073:HT29 Cells; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism* / Q000502:physiology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; C406767:IL26 protein, human; D007378:Interleukins; D020033:Protein Isoforms; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016753:Interleukin-10; C422042:interleukin 20