Interleukin-1 receptor-like 1 (IL1RL1) (ST2)

Interleukin-1 receptor-like 1 (IL1RL1), widely known as ST2, is a member of the interleukin-1 receptor family and the primary receptor for the alarmin cytokine interleukin-33 (IL-33) (UniProt P14778; Schmitz et al., 2005, Immunity). It is expressed in two major forms: a membrane-bound isoform (ST2L) that mediates transmembrane signaling and a soluble decoy isoform (sST2) that sequesters IL-33 to limit its activity (Sanada et al., 2007, J Clin Invest). ST2L signaling is crucial for the activation of Th2 cells, mast cells, and group 2 innate lymphoid cells (ILC2s), driving allergic inflammation and tissue remodeling (Liew et al., 2010, Nat Rev Immunol). In the cardiovascular system, the IL-33/ST2 axis acts as a mechanical stress sensor, where sST2 serves as a clinically significant biomarker for heart failure and myocardial infarction (Weinberg et al., 2002, Circulation; Januzzi et al., 2007, J Am Coll Cardiol). Therapeutic strategies focusing on ST2 involve monoclonal antibodies, such as astegolimab, which block the receptor to treat chronic inflammatory diseases like asthma and COPD (Kelsen et al., 2021, Lancet Respir Med).

Other names

ST2T1DER4FIT-1Interleukin-33 receptorIL33RIL1RL1

Monoclonal antibody antagonist that binds to the ST2 receptor, preventing the binding of IL-33 and subsequent recruitment of the IL-1RAcP accessory protein, thereby blocking NF-κB and MAPK signaling pathways (Schmitz et al., 2005, Immunity; Kelsen et al., 2021, Lancet Respir Med).