Interleukin 33

Interleukin 33 also known as IL-33 is a is_associated_with::protein that in humans is encoded by the IL33 is_associated_with::gene.

IL-33 is a member of the IL-1 family that potently drives production of T helper-2 (Th2)-associated is_associated_with::cytokines (e.g., IL-4). IL33 is a ligand for IL33R (is_associated_with::IL1RL1), an IL-1 family receptor that is highly expressed on is_associated_with::Th2 cells, is_associated_with::mast cells and group 2 innate lymphocytes.

IL-33 is expressed on a wide variety of cell types, including fibroblasts, mast cells, dendritic cells, macrophages, osteoblasts, endothelial cells, and epithelial cells.

Function
Interleukin 33 (IL-33) is a is_associated_with::cytokine belonging to the IL-1 superfamily. IL-33 induces is_associated_with::helper T cells, is_associated_with::mast cells, is_associated_with::eosinophils and is_associated_with::basophils to produce type 2 cytokines. This cytokine was previously named NF-HEV 'nuclear factor (NF) in high is_associated_with::endothelial is_associated_with::venules' (HEVs) since it was originally identified in these specialized cells. IL-33 mediates its biological effects by interacting with the receptors ST2 (also known as is_associated_with::IL1RL1) and IL-1 Receptor Accessory Protein (is_associated_with::IL1RAP), activating intracellular molecules in the is_associated_with::NF-κB and is_associated_with::MAP kinase signaling pathways that drive production of type 2 cytokines (e.g. IL-5 and IL-13) from polarized Th2 cells. The induction of type 2 cytokines by IL-33 in vivo is believed to induce the severe is_associated_with::pathological changes observed in is_associated_with::mucosal organs following administration of IL-33.

Structure
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.