IL33

IL33, also known as interleukin‑33, is a cytokine that belongs to the IL1 family. It is encoded by the IL33 gene located on chromosome 9p24.3 in humans. The IL33 protein is produced as a 30 kDa precursor that can be cleaved into a 18 kDa mature form by caspase‑1 or extracellular proteases. IL33 functions primarily as an “alarmin” released upon cellular damage, and it signals through a receptor complex composed of the interleukin‑1 receptor‑like 1 (IL1RL1, also called ST2) and interleukin‑1 receptor accessory protein (IL1RAcP). Binding to this complex activates downstream pathways such as NF‑κB, MAP kinases, and PI3K/AKT, leading to the production of pro‑inflammatory and Th2‑skewing cytokines.

The gene is expressed in a variety of cell types, including epithelial cells, endothelial cells, fibroblasts, and certain immune cells such as mast cells and basophils. IL33 plays a role in innate and adaptive immunity, contributing to allergic inflammation, asthma, atopic dermatitis, and certain autoimmune disorders. It also has functions in tissue repair and fibrosis, and can influence the expansion of regulatory T cells. Elevated IL33 levels have been observed in serum and tissue samples from patients with asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, and cardiovascular disease, suggesting its potential as a biomarker.

Therapeutic strategies targeting IL33 or its receptor ST2 are under investigation. ST2 antagonists and neutralizing antibodies against IL33 are being evaluated in clinical trials for asthma and other inflammatory conditions. Overall, IL33 is a multifunctional cytokine central to the regulation of immune responses and currently an active focus of clinical research.