IL33ST2

IL33ST2, also known as interleukin-33 receptor subunit ST2 or IL1RL1, is a gene that encodes the receptor for interleukin-33 (IL-33). The gene generates multiple isoforms through alternative splicing, including the transmembrane receptor ST2L, which transmits signals upon IL-33 binding, and the soluble decoy receptor sST2, which can sequester IL-33 and limit its activity.

Mechanism of action: IL-33 binds to ST2L on the cell surface and recruits the IL-1 receptor accessory protein (IL-1RAcP) to form a signaling complex that activates the MyD88-dependent pathway, leading to activation of NF-κB and MAP kinases and downstream production of type 2 cytokines such as IL-4, IL-5, and IL-13, promoting Th2 responses and eosinophil recruitment.

Expression and function: ST2 is expressed in a variety of immune and non-immune cells, including mast cells, Th2 cells, regulatory T cells, endothelial cells, and cardiac fibroblasts. The IL-33/ST2 axis plays roles in defense against helminths, tissue repair, and inflammatory responses. Its activity is context-dependent and can contribute to both protective and pathogenic outcomes.

Clinical relevance: Elevated soluble ST2 (sST2) serves as a biomarker in cardiovascular diseases, especially heart failure, where higher levels correlate with worse prognosis. Genetic variation near IL1RL1 has been associated with susceptibility to allergic diseases and asthma in some populations. The axis is a focus of research for potential therapies in asthma, atopic dermatitis, and cardiovascular disease.

See also: IL-33, ST2, IL1RL1, interleukin-1 receptor family.