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Symbol IL33 contributors: mct/npt/pgu - updated : 27-02-2017
HGNC name interleukin 33
HGNC id 16028
Location 9p24.1      Physical location : 6.241.677 - 6.257.982
Genatlas name Alarmin
Synonym name
  • DVS27-related protein
  • chromosome 9 open reading frame 26 (NF-HEV)
  • interleukin-1 family member 11
  • nuclear factor from high endothelial venules
  • Synonym symbol(s) DVS27, NFEHEV, DKFZp586H0523, C9orf26, IL1F11, NFHEV, RP11-575C20.2, IL-33
    TYPE functioning gene
    STRUCTURE 42.83 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
  • a novel exon 2E is included in the alternatively spliced messenger RNAs and, it contains an open reading frame of 131 amino acids coding for a possible transmembrane protein (PMID: 23261461)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2644 30 270 - 2007 17185418
    7 - 2592 - 228 - 2007 17185418
    5 - 2340 - 144 - 2007 17185418
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte
    not specificfibroblast
    not specificmast cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
    isoforms Precursor synthesized as a 30-kDa precursor (pro-IL-33). Pro-IL-33 is cleaved by caspase-1 into an 18-kDa mature form (mature IL-33)
  • IL1 cytokine family
  • CATEGORY secretory
    text in the absence of pro-inflammatory stimuli, localizes to the nucleus
    basic FUNCTION
  • may be involved in lung macrophage activation in clinical asthma
  • CASP1, CASP8, and calpain are dispensable for IL33 release by macrophages
  • host-protective against helminth infection and reduces atherosclerosis by promoting TH2-type immune responses
  • may function as an endogenous danger signal or alarmin, similar to IL1A and HMGB1
  • with its receptor, IL1RL1, may play important roles in eosinophil-mediated inflammation
  • prevents cardiomyocyte apoptosis and improves cardiac function and survival after MI through IL1RL1 signaling
  • have an important role in sensing damage in various infectious and inflammatory diseases
  • may be an important cytokine in the initiation and perpetuation of inflammation
  • crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses
  • seems to play a critical role in various types of innate-type inflammation in the lung and gut, whereas it is dispensable for acquired immune responses
  • crucial as an alarmin for innate-type, but not acquired-type, tissue injury-related inflammatory responses such as LPS-induced endotoxin shock
  • nuclear IL33 sequesters nuclear NFKB and reduces NFKB-triggered gene expression to dampen proinflammatory signaling
  • proteolytic processing may play an important role in the regulation of IL33 activity during inflammation
  • in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of RELA
  • dual-function molecule that regulates gene expression in nuclei and, as a cytokine, conveys proinflammatory signals from outside of cells via its specific receptor IL1RL1
  • IL33/IL1RL1 signaling plays an important role in regulating IL33 induced inflammatory responses in ocular surface
  • may play a pivotal role in maintenance of cutaneous homeostasis and acceleration of normal wound healing
  • predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation
  • IL33, may induce inflammatory molecule release from the glial cells and may play an important role in the pathogenesis of Alzheimer disease
  • acts as an immunoadjuvant to enhance antigen-specific tumor immunity
  • contributes to disease processes in association with Th1 and Th2 phenotypes
  • cell-intrinsic role for the IL33/IL1RL1 axis in the regulation of apoptosis in mast cellls, identifying thereby a previously unappreciated pathway supporting expansion of the mast cellls population with inflammation
  • IL33/IL1RL1 axis plays an essential role in the development of visceral adipose tissue Treg (VAT-Treg) cells
  • IL33 and IL1RL1 function as a developmental switch to license thermogenesis during the perinatal period
  • IL33/IL1RL1 pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGFA in tumor cells and attenuating tumor necrosis
  • IL33/IL1RL1 signaling may be involved in periapical inflammation and tissue fibrosis
  • a component
    small molecule
  • ligand for the then orphan receptor IL1RL1
  • likely dual functions (activation/termination) of PRTN3 in IL33 biological activity
  • processed into mature bioactive forms by neutrophil elastase and cathepsin G
  • endothelial nuclear IL33 is induced by NOTCH1 and DLL4 may be the dominant ligand responsible for this signaling
  • TMED1 is required for optimal IL33-induced IL8 and IL6 production
  • IFNG induces IL33 in keratinocytes and IL33 acts on activated T cells to further increase the release of IFNG, therefore contributing to drive skin inflammation towards chronic responses
  • signals through its ligand-binding primary receptor IL1RL1 and IL1 receptor accessory protein (IL1RAP)
  • IFNG directly controls IL33 protein level through a STAT1- and PSMB9-dependent mechanism
  • upregulation of CSF2 and CSF1 production by endothelial cells, an effect that appears to be mediated by NFKB1 and to be independent of IL1, may be an additional mechanism through which IL33 contributes to inflammatory activation of the vessel wall
  • PIBF1 expression by B cells is induced by the mucosal alarmin IL33
  • cell & other
    induced by by IL17A in epidermal keratinocytes, may be involved in the pathophysiology of inflammatory skin diseases, including psoriasis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls
    constitutional     --over  
    IL33 and IL1RL1 positive cells were also significantly increased in Alzheimer disease (AD) brains when compared to non-AD brains
    constitutional     --low  
    pre-eclampsia is associated with lower serum IL33
    constitutional     --low  
    decreased levels of placental ADAMTS12 were found to be associated with intrahepatic cholestasis of pregnancy (ICP), suggesting a possible role of inflammation in the pathogenesis
    tumoral     --over  
    of IL33 expression in borderline and malignant epithelial ovarian tumours indicates its involvement in the development and progression of epithelial ovarian cancer (EOC), and its increased expression in less differentiated cancers suggests their association with poor prognosis in this category of tumours
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • could be a new target for therapeutic intervention across a range of diseases
  • SystemTypeDisorderPubmed
    may provide new therapeutic targets for controlling mucosal eosinophilic inflammation
    cardiovascularaquiredheart failure
    IL33/IL1RL1 not only represents a promising cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast-cardiomyocyte communication that may prove to be a therapeutic target for the prevention of heart failure