Suppression of tumorigenicity protein 2 (ST2)

Suppression of tumorigenicity protein 2 (ST2) is a member of the interleukin-1 receptor family and exists as both a membrane-bound functional receptor (ST2L) and a soluble decoy receptor (sST2), encoded by the IL1RL1 gene[2][5]. ST2 interacts with interleukin-33 (IL-33), which triggers or modulates downstream pathways involved in immune regulation, inflammation, tissue repair, and fibrosis[2][4][5]. The membrane-bound ST2L form is primarily expressed on immune cells such as lymphocytes, mast cells, macrophages, eosinophils, and on cardiomyocytes, mediating protective effects of IL-33 (especially in the heart), while the soluble sST2 form acts as a decoy that can inhibit IL-33’s beneficial signaling[2][4][5][6]. Elevated levels of sST2 in circulation are predictive for adverse outcomes in cardiovascular disease and other inflammatory conditions, and sST2 has been established as an important biomarker for prognosis in heart failure, myocardial infarction, and several other disorders[3][5][7]. The IL-33/ST2 signaling axis is also implicated in the pathogenesis and progression of several cancers, pulmonary diseases such as pulmonary fibrosis, and inflammatory disorders, making ST2 a biologically important therapeutic target as well as a clinically relevant biomarker[1][2][3][5].

Other names

Growth stimulation expressed gene 2IL-1 receptor-like 1 (IL1RL1)ST2L (membrane form)sST2 (soluble form)T1FIT-1DER4

Acts as a decoy receptor that binds interleukin-33 (IL-33), thereby modulating the downstream effects of IL-33 on proliferation, inflammation, and fibrosis. The membrane-bound form (ST2L) participates in IL-33 signaling leading to anti-fibrotic and anti-hypertrophic effects in the heart. The soluble form (sST2) sequesters IL-33 and attenuates its protective effects, promoting pro-fibrotic and pro-inflammatory processes in the context of excess sST2.