Abstract
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.
MeSH terms
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Animals
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / biosynthesis
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, CD / physiology*
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Autocrine Communication / immunology
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Cell Line, Tumor
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Cells, Cultured
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Cytokine Receptor gp130
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Cytokines / biosynthesis
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Cytokines / genetics
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation / immunology
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Humans
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Inflammation Mediators / metabolism
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Interleukins / antagonists & inhibitors
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Interleukins / physiology*
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Mast Cells / immunology
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Mast Cells / metabolism
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Monocytes / immunology
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Monocytes / metabolism
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NIH 3T3 Cells
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Phosphorylation
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RNA, Messenger / biosynthesis
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Receptors, Cytokine / biosynthesis
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Receptors, Cytokine / physiology*
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Receptors, Interleukin
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STAT1 Transcription Factor
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STAT3 Transcription Factor
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Signal Transduction / immunology*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / metabolism
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Transcription, Genetic / immunology
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Transcriptional Activation
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Tyrosine / metabolism
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD
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Cytokines
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DNA-Binding Proteins
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IL27RA protein, human
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IL6ST protein, human
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Il27 protein, mouse
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Il27ra protein, mouse
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Il6st protein, mouse
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Inflammation Mediators
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Interleukins
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MYDGF protein, human
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cytokine
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Receptors, Interleukin
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STAT1 Transcription Factor
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STAT1 protein, human
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat1 protein, mouse
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Stat3 protein, mouse
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Trans-Activators
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Cytokine Receptor gp130
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Tyrosine