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Title

The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33

Authors
Lipsky, Brian P.
Smithgall, Molly D.
Meininger, David
Siu, Sophia
Smith, Dirk E.
Published in Cytokine. 2008, vol. 42, no. 3, p. 358-64
Abstract Interleukin (IL)-33 (or IL-1F11) was recently identified as a ligand for the orphan IL-1 receptor family member T1/ST2 (ST2). IL-33 belongs to the IL-1 cytokine family and, upon binding to ST2, induces intracellular signals similar to those utilized by IL-1. The effects of other IL-1 family cytokines are mediated by their binding to a specific receptor and the recruitment of a co-receptor required for elicitation of signaling. The aim of this study was to characterize the co-receptor involved in IL-33 signaling. Immunoprecipitation confirmed that IL-33 specifically binds ST2 and revealed that cellular IL-1 receptor accessory protein (AcP) associates with ST2 in a ligand-dependent manner. Receptor binding measurements demonstrated that the affinity of mouse (m)IL-33 for ST2 is increased by 4-fold in presence of AcP. IL-33 dose-dependently stimulated IL-6 secretion from wild-type (WT) mast cells, while no effect of IL-33 was observed with mast cells derived from AcP-deficient mice. Finally, soluble (s)ST2-Fc and sAcP-Fc acted synergistically to inhibit IL-33 activity. These observations identify AcP as a shared co-receptor within the IL-1 family that is essential for IL-33 signaling and suggest a novel role for sAcP in modulating the activity of IL-33.
Keywords AnimalsCell Line, TumorHumansImmunoglobulin Fc Fragments/metabolismInterleukin-1 Receptor Accessory Protein/metabolismInterleukin-6/metabolismInterleukins/metabolismMast Cells/metabolismMembrane Proteins/metabolismMiceMice, Inbred C57BLProtein BindingSignal TransductionSubstrate SpecificitySurface Plasmon Resonance
Stable URL http://archive-ouverte.unige.ch/unige:1083
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Identifiers
PMID: 18450470
Structures
Research group Mécanisme de l'inflammation articulaire (44)
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