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IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.

Cytokines of the interleukin-1 (IL-1) family, such as IL-1 alpha/beta and IL-18, have important functions in host defense, immune regulation, and inflammation. Insight into their biological functions has led to novel therapeutic approaches to treat human inflammatory diseases. Within the IL-1 family, IL-1 alpha/beta, IL-1Ra, and IL-18 have been matched to their respective receptor complexes and have been shown to have distinct biological functions. The most prominent orphan IL-1 receptor is ST 2. This receptor has been described as a negative regulator of Toll-like receptor-IL-1 receptor signaling, but it also functions as an important effector molecule of T helper type 2 responses. We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.

Pubmed ID: 16286016


  • Schmitz J
  • Owyang A
  • Oldham E
  • Song Y
  • Murphy E
  • McClanahan TK
  • Zurawski G
  • Moshrefi M
  • Qin J
  • Li X
  • Gorman DM
  • Bazan JF
  • Kastelein RA



Publication Data

November 15, 2005

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cell Polarity
  • Cytokines
  • Enzyme Activation
  • Eosinophils
  • Gene Expression Regulation
  • Humans
  • Interleukins
  • Mast Cells
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • NF-kappa B
  • Phosphorylation
  • Phylogeny
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Spleen
  • Th2 Cells