WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27.
The recently discovered cytokine IL-27 belongs to the IL-6/IL-12 family of cytokines and induced proliferation of naive CD4(+) T cells and the generation of a Th1-type adaptive immune response. Although binding of IL-27 to the cytokine receptor WSX-1 was demonstrated, this interaction proved insufficient to mediate cellular effects. Hence, IL-27 was believed to form a heteromeric signaling receptor complex with WSX-1 and another, yet to be identified, cytokine receptor subunit. In this study, we describe that WSX-1 together with gp130 constitutes a functional signal-transducing receptor for IL-27. We show that neither of the two subunits itself is sufficient to mediate IL-27-induced signal transduction, but that the combination of both is required for this event. Expression analysis of WSX-1 and gp130 by quantitative PCR suggests that IL-27 might have a variety of cellular targets besides naive CD4(+) T cells: we demonstrate gene induction of a subset of inflammatory cytokines in primary human mast cells and monocytes in response to IL-27 stimulation. Thus, IL-27 not only contributes to the development of an adaptive immune response through its action on CD4(+) T cells, it also directly acts on cells of the innate immune system.
Pflanz
Stefan
S
DNAX Research Institute, Palo Alto, CA 94304, USA.
Hibbert
Linda
L
Mattson
Jeanine
J
Rosales
Rency
R
Vaisberg
Elena
E
Bazan
J Fernando
JF
Phillips
Joseph H
JH
McClanahan
Terrill K
TK
de Waal Malefyt
Rene
R
Kastelein
Robert A
RA
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019898:Autocrine Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000502:physiology*; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D004268:DNA-Binding Proteins; C112441:IL27RA protein, human; C494199:IL6ST protein, human; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; C494200:Il6st protein, mouse; D018836:Inflammation Mediators; D007378:Interleukins; C464565:MYDGF protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D014443:Tyrosine