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

Cytokine. 2008 Jun;42(3):358-64. doi: 10.1016/j.cyto.2008.03.008. Epub 2008 May 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Interleukin-1 Receptor Accessory Protein / metabolism*
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-6 / metabolism
  • Interleukins / metabolism*
  • Mast Cells / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding
  • Receptors, Interleukin
  • Signal Transduction*
  • Substrate Specificity
  • Surface Plasmon Resonance


  • IL33 protein, human
  • Il1rap protein, mouse
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Immunoglobulin Fc Fragments
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-6
  • Interleukins
  • Membrane Proteins
  • Receptors, Interleukin