IL33
Description
The IL33 (interleukin 33) is a protein-coding gene located on chromosome 9.
Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene. It is a member of the IL-1 family and potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL-4). IL-33 is a ligand for ST2 (IL1RL1), an IL-1 family receptor 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. Its β-trefoil structure is 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.
IL33 binds to and signals through the IL1RL1/ST2 receptor, activating NF-kappa-B and MAPK signaling pathways in target cells. It is involved in the maturation of Th2 cells, inducing the secretion of T-helper type 2-associated cytokines. IL33 also activates mast cells, basophils, eosinophils and natural killer cells. It enhances the polarization of alternatively activated macrophages and acts as a chemoattractant for Th2 cells. IL33 may function as an 'alarmin', amplifying immune responses during tissue injury. It induces rapid UCP2-dependent mitochondrial rewiring, attenuating the generation of reactive oxygen species and preserving the integrity of the Krebs cycle, which is required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages.
IL33 is also known as C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV.
