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

Immunity. 2005 Nov;23(5):479-90. doi: 10.1016/j.immuni.2005.09.015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cell Polarity
  • Cytokines / genetics
  • Cytokines / immunology*
  • Enzyme Activation
  • Eosinophils / cytology
  • Eosinophils / metabolism
  • Gene Expression Regulation
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / chemistry
  • Interleukins / classification
  • Interleukins / genetics
  • Interleukins / immunology*
  • Mast Cells / metabolism
  • Membrane Proteins / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Phosphorylation
  • Phylogeny
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1 / immunology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • Cytokines
  • IL1RL1 protein, human
  • IL33 protein, human
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Mitogen-Activated Protein Kinases