Disease relevance of IL33

• Accordingly, in situ hybridization demonstrated that endothelial cells constitute a major source of IL-33 mRNA in chronically inflamed tissues from patients with rheumatoid arthritis and Crohn's disease [1].
• IL-28 reacted with 4 of 15 and IL-33 with 2 of 15 Hashimoto's thyroiditis serum samples (antimicrosomal antibody titers, greater than 1:6400) [2].

High impact information on IL33

• 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 [3].
• The cytokine IL-33 is the specific ligand for ST2 [4].
• Together, these data suggest that, similarly to IL1alpha and HMGB1, IL-33 is a dual function protein that may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties [1].
• Here, we show that IL-33, an IL-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines, is an endothelium-derived, chromatin-associated nuclear factor with transcriptional repressor properties [1].
• Nuclear localization, heterochromatin-association, and targeting to mitotic chromosomes were all found to be mediated by an evolutionarily conserved homeodomain-like helix-turn-helix motif within the IL-33 N-terminal part [1].

Biological context of IL33

• Finally, IL-33 was found to possess transcriptional repressor properties, associated with the homeodomain-like helix-turn-helix motif [1].
• A full-length cDNA for the unknown clone DVS 27, whose expression was most highly upregulated, was isolated from the cerebral artery cDNA library by hybridization [5].
• Lysate from clones IL-28 and IL-33 did not reduce the antimicrosomal antibody titer in a hemagglutination assay [2].
• On the other hand, IL-28 and IL-29 are considered to be critical for mounting an efficient antiviral response and IL-32 and IL-33, which are yet to be fully characterized, are emerging as important components of the inflammatory response in allergy and autoimmunity [6].

Anatomical context of IL33

• Immunostaining with three distinct antisera, directed against the N-terminal part and IL-1-like C-terminal domain, revealed that IL-33 is a heterochromatin-associated nuclear factor in HEV endothelial cells in vivo [1].
• We found that IL-33 is identical to NF-HEV, a nuclear factor preferentially expressed in high endothelial venules (HEV), that we previously characterized [1].

References