Abstract
IL-33 (IL-1F11) is a recently described member of the IL-1 family of cytokines that stimulates the generation of cells, cytokines, and Igs characteristic of a type 2 immune response. IL-33 mediates signal transduction through ST2, a receptor expressed on Th2 and mast cells. In this study, we demonstrate that IL-33 and ST2 form a complex with IL-1R accessory protein (IL-1RAcP), a signaling receptor subunit that is also a member of the IL-1R complex. Additionally, IL-1RAcP is required for IL-33-induced in vivo effects, and IL-33-mediated signal transduction can be inhibited by dominant-negative IL-1RAcP. The implications of this shared usage of IL-1RAcP by IL-1(alpha and beta) and IL-33 are discussed.
MeSH terms
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Animals
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Gene Expression Regulation / immunology
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Genes, Dominant / immunology
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Interleukin-1 Receptor Accessory Protein / deficiency
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Interleukin-1 Receptor Accessory Protein / immunology*
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-1alpha / genetics
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Interleukin-1alpha / immunology
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Interleukin-33
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Interleukins / genetics
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Interleukins / immunology*
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Mast Cells / cytology
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Mast Cells / immunology*
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Mice
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Mice, Knockout
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Multiprotein Complexes / genetics
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Multiprotein Complexes / immunology*
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Protein Subunits / genetics
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Protein Subunits / immunology
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Receptors, Interleukin
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Th2 Cells / cytology
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Th2 Cells / immunology*
Substances
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Il1rap protein, mouse
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Il1rl1 protein, mouse
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Il33 protein, mouse
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Interleukin-1 Receptor Accessory Protein
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-1alpha
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Interleukin-1beta
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Interleukin-33
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Interleukins
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Membrane Proteins
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Multiprotein Complexes
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Protein Subunits
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Receptors, Interleukin