interleukin33

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family of cytokines, a group of signaling proteins that play a critical role in the immune system. First identified in 2005, IL-33 is produced primarily by epithelial cells, endothelial cells, and certain immune cells, including fibroblasts and dendritic cells. It acts as an alarmin, meaning it is released upon cell damage or stress, serving as a danger signal to initiate immune responses.

IL-33 binds to its receptor, the interleukin-1 receptor-like 1 (IL-1RL1), also known as ST2, which forms a complex with the IL-1 receptor accessory protein (IL-1RAcP). This interaction triggers signaling pathways that promote inflammation, particularly through the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs). These pathways enhance the production of pro-inflammatory cytokines, such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), which are involved in type 2 immune responses.

IL-33 has been implicated in various immune-mediated diseases, including asthma, allergic inflammation, and autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus. It also plays a role in tissue repair and fibrosis, as well as in the regulation of Th2 and Th17 cell differentiation, which are key subsets of helper T cells. Additionally, IL-33 has been studied in the context of cancer, where it can influence tumor progression and immune evasion.

Research on IL-33 continues to explore its dual role as both a pro-inflammatory mediator and a regulator of tissue homeostasis, offering potential therapeutic targets for inflammatory and autoimmune diseases. Its complex functions highlight the intricate balance required in immune system regulation.