Interleukin 33

Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene. Interleukin 33 is a member of the IL-1 family that potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL-4). IL33 is a ligand for ST2 (IL1RL1), an IL-1 family receptor that is highly expressed on Th2 cells, mast cells and group 2 innate lymphocytes. IL-33 is expressed by a wide variety of cell types, including fibroblasts, mast cells, dendritic cells, macrophages, osteoblasts, endothelial cells, and epithelial cells. IL-33 is a member of the IL-1 superfamily of cytokines, a determination based in part on the molecules β-trefoil structure, a conserved structure type described in other IL-1 cytokines, including IL-1α, IL-1β, IL-1Ra and IL-18. In this structure, the 12 β-strands of the β-trefoil are arranged in three pseudorepeats of four β-strand units, of which the first and last β-strands are antiparallel staves in a six-stranded β-barrel, while the second and third β-strands of each repeat form a β-hairpin sitting atop the β-barrel. IL-33 is a ligand that binds to a high-affinity receptor family member ST2. The complex of these two molecules with IL-1RAcP indicates a ternary complex formation. The binding area appears to be a mix of polar and non-polar regions that create a specific binding between ligand and receptor. The interface between the molecules has been shown to be extensive. Structural data on the IL-33 molecule was determined by solution NMR and small angle X-ray scattering. Interleukin 33 (IL-33) is a cytokine belonging to the IL-1 superfamily. IL-33 induces helper T cells, mast cells, eosinophils and basophils to produce type 2 cytokines. This cytokine was previously named NF-HEV 'nuclear factor (NF) in high endothelial venules' (HEVs) since it was originally identified in these specialized cells. IL-33 acts intracellularly as a nuclear factor and extracellularly as a cytokine. IL-33 is constitutively located in the nucleus of structural cells of humans and mice and has a helix-turn-helix domain presumably allowing it to bind to DNA.