IL1RL1

IL1RL1, also known as ST2, is a member of the interleukin-1 receptor (IL-1R) superfamily. The IL1RL1 gene encodes several isoforms, with the principal transmembrane receptor being ST2L and a soluble form referred to as soluble ST2 (sST2) produced by alternative splicing. The receptor binds the cytokine interleukin-33 (IL-33). For signaling, ST2L forms a receptor complex with the IL-1 receptor accessory protein (IL-1RAcP).

Signaling through the IL-33/ST2L axis activates MyD88-dependent pathways, leading to NF-κB and MAPK activation and the production of inflammatory mediators, including Th2-associated cytokines such as IL-4, IL-5, and IL-13. ST2 is expressed by a variety of cell types, including mast cells, CD4+ Th2 cells, group 2 innate lymphoid cells (ILC2s), endothelial cells, and fibroblasts, and IL-33 is released as an alarmin upon cellular damage or stress.

Soluble ST2 acts as a decoy receptor that sequesters IL-33, dampening signaling through ST2L. The IL-33/ST2 axis thus participates in both protective and pathogenic responses, contributing to allergic and inflammatory diseases as well as tissue repair processes. In cardiovascular contexts, sST2 serves as a clinically useful biomarker, with elevated serum levels associated with worse outcomes in heart failure and acute myocardial infarction.

Genetics and regulation: IL1RL1 is located on chromosome 2q12 and yields multiple transcript variants. Polymorphisms and regulatory mechanisms of IL1RL1 influence susceptibility to asthma and other atopic disorders, reflecting the axis’s role in coordinated immune responses.

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