Anti-IL-33 Monoclonal Antibody

IL-33, also known as NF-HEV and DVS 27, is a 30 kDa proinflammatory protein that may also regulate gene transcription. DVS 27 was identifed as a gene that is upregulated in vasospastic cerebral arteries. NF-HEV was described as a nuclear factor that is preferentially expressed in the endothelial cells of high endothelial venules relative to endothelial cells from other tissues. IL-33 was identified based on sequence and structural homology with IL-1 family cytokines. DVS 27, NF-HEV, and IL-33 share 100% amino acid sequence identity. IL-33 is constitutively expressed in smooth muscle and airway epithelia. It is upregulated in arterial smooth muscle, dermal fibroblasts, and keratinocytes following IL-1 alpha or IL-1 beta stimulation. Similar to IL-1, IL-33 can be cleaved in vitro by caspase-1, generating an N-terminal fragment that is slightly shorter than the C-terminal fragment. The N-terminal portion of full length IL-33 contains a predicted bipartite nuclear localization sequence and a homeodomain-like helix-turn-helix DNA binding domain. By immunofluorescence, full length IL-33 localizes to the nucleus in HUVECs and transfectants. The C-terminal fragment, corresponding to mature IL-33, binds and triggers signaling through mast cell IL-1 R4/ST2L, a longtime orphan receptor involved in the augmentation of Th2 cell responses. A ternary signaling complex is formed by the subsequent association of IL-33 and ST2L with IL-1R AcP. Stimulation of Th2 polarized lymphocytes with mature IL-33 in vitro induces IL-5 and IL-13 secretion. In vivo administration of mature IL-33 promotes increased production of IL-5, IL-13, IgE, and IgA, as well as splenomegaly and inflammatory infiltration of mucosal tissues. Full length and mature human IL-33 share 52 - 58% aa sequence identity with mouse and rat IL-33. Human IL-33 shares less than 20% aa sequence identity with other IL-1 family proteins. Protein function: Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016, PubMed:19841166). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2- associated cytokines (PubMed:17853410, PubMed:18836528). Also involved in activation of mast cells, basophils, eosinophils and natural killer cells (PubMed:17853410, PubMed:18836528). Acts as an enhancer of polarization of alternatively activated macrophages (PubMed:19841166). Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury (PubMed:17853410, PubMed:18836528). Induces rapid UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages. [The UniProt Consortium]