ST2

ST2, also known as suppression of tumorigenicity 2, is a protein that belongs to the interleukin-1 receptor family. The ST2 gene is encoded by IL1RL1 and produces two main isoforms: a transmembrane receptor called ST2L and a soluble form known as sST2. ST2 binds the cytokine interleukin-33 (IL-33), with ST2L forming a receptor complex together with the IL-1 receptor accessory protein to initiate intracellular signaling. The soluble form, sST2, can bind IL-33 and act as a decoy receptor, reducing IL-33 availability for signaling.

Biologically, ST2 is expressed in multiple cell types, including mast cells, T helper 2 cells, eosinophils, and various cells in the heart and cardiovascular system. IL-33/ST2 signaling influences inflammatory and immune responses, often promoting Th2-skewed immunity and tissue repair processes. In the cardiovascular context, the IL-33/ST2 axis can exert cardioprotective effects under stress, while circulating sST2 can dampen these signals by sequestering IL-33.

Clinical significance is most strongly observed with sST2 as a biomarker. Elevated serum sST2 levels are associated with worse prognosis in heart failure and acute myocardial injury, aiding risk stratification and management decisions in some clinical settings. The balance between ST2L signaling and sST2-mediated sequestration of IL-33 is a focus of ongoing research, with implications for inflammatory diseases, allergy, and cardiovascular pathology.

In summary, ST2 is a dual-form receptor involved in immune regulation and cardiovascular homeostasis, acting through the IL-33 signaling axis and modulated by its soluble decoy form.