IL33
GeneName
IL33
Summary
IL33, also known as Interleukin-33, is a 31kDa cytokine that plays a pivotal role in the immune response. It is expressed in various tissues, including epithelial cells and immune cells, and is found in both the cytoplasm and extracellular space. IL33 functions by binding to its receptor, which initiates signalling pathways involved in the regulation of immune responses. It is implicated in processes such as macrophage differentiation, microglial cell activation, and the regulation of cytokine production, particularly in the context of type 2 immune responses and inflammation.
Importance
IL33 is relevant to: - The modulation of allergic responses and asthma through its role in promoting Th2 cell differentiation and cytokine production - The regulation of innate immune responses, particularly in the context of infections and tissue damage - Neuroinflammation and its potential involvement in neurodegenerative diseases, as it influences microglial activation - The development of therapeutic strategies targeting IL33 or its receptor in various inflammatory and autoimmune conditions
Top Products
For researchers investigating IL33, we highly recommend the top-selling recombinant antibody, Anti-IL-33 antibody [EPR20417] (ab207737). This antibody has been validated for use in immunohistochemistry (IHC) and western blotting (WB), making it a versatile tool for various experimental needs. With 12 citations, it is gaining recognition in the research community for its reliability and performance. This recombinant antibody ensures batch-to-batch consistency, providing confidence in your results as you explore the role of IL33 in your studies. The Human IL-33 ELISA Kit (ab223865), supported by 8 citations, is an excellent option for researchers looking to accurately measure IL-33 levels in their samples.
Abcam Product Citation Summary
The data indicates that IL33 is being studied in the context of renal damage and profibrosis, as well as its role in MHC-I expression. The use of the same antibody in multiple studies suggests a consistent interest in the role of IL33 in these biological processes.
Abcam Product Citation Table
Domain
The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.
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 (By similarity).
In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets (PubMed:21734074). This form is rapidely lost upon angiogenic or pro-inflammatory activation (PubMed:18787100).
Post-translational modifications
The full-length protein can be released from cells and is able to signal via the IL1RL1/ST2 receptor. However, proteolytic processing by CELA1, CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal peptides that are more active than the unprocessed full length protein (PubMed:22307629, PubMed:35794369). May also be proteolytically processed by calpains (PubMed:19596270, PubMed:22307629). Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation (PubMed:19559631). In vitro proteolytic cleavage by CASP1 was reported (PubMed:16286016, PubMed:19439663) but could not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is probably not a direct substrate for that caspase (PubMed:19439663, PubMed:19465481).
Sequence Similarities
Belongs to the IL-1 family. Highly divergent.
Tissue Specificity
Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Cytoplasmic vesicle
- Secretory vesicle
- Secreted
- Secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore following cleavage by CELA1 (PubMed:35794369). Associates with heterochromatin and mitotic chromosomes (PubMed:17185418). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059).
Alternative names
C9orf26, IL1F11, NFHEV, IL33, Interleukin-33, IL-33, Interleukin-1 family member 11, Nuclear factor from high endothelial venules, IL-1F11, NF-HEV
Database links
swissprot:O95760 omim:608678 entrezGene:90865
Other research areas
- Cardiovascular
- Immuno-oncology