en
Scientific article
English

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

Published inCytokine, vol. 42, no. 3, p. 358-364
Publication date2008
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
  • Animals
  • Cell Line, Tumor
  • Humans
  • Immunoglobulin Fc Fragments/metabolism
  • Interleukin-1 Receptor Accessory Protein/metabolism
  • Interleukin-6/metabolism
  • Interleukins/metabolism
  • Mast Cells/metabolism
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding
  • Signal Transduction
  • Substrate Specificity
  • Surface Plasmon Resonance
Citation (ISO format)
PALMER-LOURENCO, Gaby et al. 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. In: Cytokine, 2008, vol. 42, n° 3, p. 358–364. doi: 10.1016/j.cyto.2008.03.008
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Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal1096-0023
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