Interleukin 33

Interleukin 33 (IL-33) is a 270 amino acid protein in humans. The protein contains an N-terminal nuclear localization signal (NLS), a helix-turn-helix (HTH) motif, and a C-terminal region with structural homology to the IL-1 family of cytokines. The protein is proteolytically converted by CASP-1 into a 18 kDa C-terminal mature form which functions as a cytokine. The protein is abundantly expressed in high endothelial venules found in tonsils, Peyer’s patches and mesenteric lymph nodes. The C-terminal fragment of IL-33 is the only cytokine that has been shown to bind the receptor ST2L. The IL-33/ST2L complex subsequently associates with IL-1R AcP thereby activating intracellular molecules in the NF-kB and MAP kinase signaling pathways. This activation drives the production of type 2 cytokines from polarized Th2 cells. The induction of these cytokines (e.g. IL-5 and IL-13) by IL-33 in vivo is believed to cause severe pathological changes observed in mucosal organs.

It has recently been shown that dying cells caused by a viral infection in spleen and lymph nodes release IL-33 that notifies CD8+ T cells (CTLs) of the focus of infection. IL-33 is the principal alarm in discharged from the dying cells, and is necessary for a potent CTL response to replicating viruses. Mice deficient in IL-33 displayed a reduced CTL response to viral infections.