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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2005-11, Vol.23 (5), p.479-490
• Main Authors: Schmitz, Jochen, Owyang, Alexander, Oldham, Elizabeth, Song, Yaoli, Murphy, Erin, McClanahan, Terril K., Zurawski, Gerard, Moshrefi, Mehrdad, Qin, Jinzhong, Li, Xiaoxia, Gorman, Daniel M., Bazan, J. Fernando, Kastelein, Robert A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cell Differentiation; Cell Polarity; Chromosomes; Cytokines - genetics; Cytokines - immunology; Enzyme Activation; Eosinophils - cytology; Eosinophils - metabolism; Gene expression; Gene Expression Regulation; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins - chemistry; Interleukins - classification; Interleukins - genetics; Interleukins - immunology; Kinases; Ligands; Mast Cells - metabolism; Membrane Proteins - immunology; Mice; Mitogen-Activated Protein Kinases - metabolism; Molecular Sequence Data; NF-kappa B - metabolism; Phosphorylation; Phylogeny; Proteins; 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; Transcription factors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2005.09.015

Cytokines of the interleukin-1 (IL-1) family, such as IL-1α/β 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-1α/β, 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 ST2. 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 ST2, activates NF-κB and MAP kinases, and drives production of TH2-associated cytokines from in vitro polarized TH2 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.