Human Interleukin 33 (IL33) Protein

Background

IL33 is a nuclear alarmin cytokine belonging to the IL-1 family, released during cellular stress, injury, or necrosis to alert the immune system and promote inflammation. IL33 binds to its receptor IL1RL1 (ST2) and forms a signaling complex with IL1RAP, leading to activation of NF-κB and MAPK pathways, which drive cytokine production, immune cell activation, and tissue repair. IL33 primarily targets type 2 immune cells, including Th2 cells, innate lymphoid cells (ILC2s), mast cells, and eosinophils, to regulate allergic inflammation, tissue homeostasis, and anti-helminth immunity. It is abundantly expressed in epithelial cells, endothelial cells, and fibroblasts, where it functions as both a cytokine and a transcriptional regulator. Dysregulated IL33 signaling contributes to allergic diseases, such as asthma, atopic dermatitis, and rhinitis, as well as inflammatory and fibrotic disorders. In tumors, IL33 can promote both pro- and anti-tumor immune responses depending on the context. Knockout studies reveal reduced type 2 cytokine production, impaired tissue repair, and weakened immune responses, highlighting IL33’s role in inflammation, tissue homeostasis, and immunity.