Structural data on the IL-33 molecule was determined by solution NMR and small angle X-ray scattering.
This cytokine was previously named NF-HEV 'nuclear factor (NF) in high endothelial venules' (HEVs) since it was originally identified in these specialized cells.
Alarmins, also known as danger-associated molecular patterns (DAMPs), are endogenous molecules that are released by stressed, damaged, or dying cells.
IL-33 released from damaged tissue during viral infection directly stimulates cytotoxic CD8+ T cells for the efficient generation of a memory–recall response and antiviral immunity.
[10][11] IL-33 is constitutively located in the nucleus of structural cells of humans and mice[12] and has a helix-turn-helix domain[9] presumably allowing it to bind to DNA.
The induction of type 2 cytokines by IL-33 in vivo is believed to induce the severe pathological changes observed in mucosal organs following administration of IL-33.
The oxidation process results in the formation of two disulphide bridges and a change in the conformation of the molecule, which prevents it from binding to its receptor, ST2.
[27] Risk “T” rs4742170 allele disrupts binding of GR transcription factor to IL33 putative enhancer that may explain the negative effect of the rs4742170 (T) risk allele on the development of wheezing phenotype that strongly correlates with allergic sensitization in childhood.
The IL-33 protein resides in keratinocytes of the skin and when subjected to irritation or allergic conditions will communicate with nearby sensory neurons and initiate an itchy feeling.
[32] In mice, IL-33 was found to effect the production of methionine-enkephalin peptides in group 2 innate lymphocytes, in turn promoting the emergence of beige adipocytes, which leads to increased energy expenditure and decreased adiposity.
[38] In a mouse model of chronic asthma, anti-IL-33 administration decreased antigen-induced immune response.
[41] This article incorporates text from the United States National Library of Medicine, which is in the public domain.