IL1RL1 Gene: Function, Expression, and Clinical Significance

IL1RL1 (Interleukin 1 Receptor Like 1) encodes a member of the interleukin 1 receptor family, also known as ST2. The protein is a receptor for interleukin-33 (IL-33) and plays a critical role in type 2 immune responses, including allergic inflammation, asthma, and fibrosis. Alternative splicing generates multiple isoforms, including a transmembrane receptor (ST2L) and a soluble decoy receptor (sST2). The gene is located on chromosome 2q12.1 and is expressed in various immune cells, epithelial cells, and fibroblasts.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• IL-33/ST2 signaling pathway

• Th2 differentiation pathway

• Asthma and allergic inflammation pathway

• IL-1 family signaling pathway

The IL1RL1 protein (ST2) is a transmembrane receptor that binds interleukin-33 (IL-33) with high affinity. Upon IL-33 binding, ST2 recruits the adaptor protein MyD88 and activates NF-κB and MAP kinase pathways, leading to production of type 2 cytokines (e.g., IL-4, IL-5, IL-13). The soluble isoform (sST2) lacks the transmembrane domain and acts as a decoy receptor, modulating IL-33 bioavailability. ST2 is expressed on Th2 cells, mast cells, eosinophils, basophils, group 2 innate lymphoid cells (ILC2s), and various structural cells. It is a key mediator of allergic inflammation and a clinically validated biomarker for asthma exacerbation and heart failure.