IL33 gene

The IL33 gene (IL33 stands for: Interleukin 33) is a protein-coding gene located on chromosome 9p24.1. Several transcript variants encoding different isoforms have been found for this gene.

The protein of the same name encoded by the IL33 gene(interleukin-33) is a cytokine that binds to the IL1RL1/ST2 receptor and sends out signals via this receptor, which in turn activate NF-kappa-B and MAPK signaling pathways in the target cells. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells.

Cytokine that binds to the IL1RL1/ST2 receptor and sends signals via this receptor, which in turn activate NF-kappa-B and MAPK signaling pathways in the target cells. The cytokine is involved in the maturation of Th2 cells, which trigger the secretion of T helper type 2-associated cytokines (Schmitz J et al. 2005). Also involved in the activation of mast cells, basophils, eosinophils and natural killer cells (Moussion C et al. 2008). Acts as an enhancer of polarization of alternatively activated macrophages. Acts as a chemoattractant for Th2 cells and may act as an"alarmin" that enhances immune responses to tissue injury (Komai-Koma M et al. 2007). Induces rapid UCP2-dependent mitochondrial switching that attenuates reactive oxygen species generation and preserves the integrity of the Krebs cycle, which is required for the sustained production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages.

In quiescent endothelia, the uncleaved form is constitutively and abundantly expressed and acts as a chromatin-associated nuclear factor with transcriptional repressor properties. It can sequester nuclear NF-kappaB/RELA and thus reduce the expression of its targets (Ali S et al. 2011) This form is rapidly lost upon angiogenic or proinflammatory activation.

Diseases associated with IL33 include autoimmune pancreatitis and granulomatous mastitis.

1. Ali S et al. (2011) The dual function cytokine IL-33 interacts with the transcription factor NF-κB to dampen NF-κB-stimulated gene transcription. J Immunol 187:1609-1616.
2. Komai-Koma M et al. (2007) IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol 37:2779-2786.
3. Moussion C et al. (2008) The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One 3:e3331.
4. Schmitz J et al. (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479-490.