Interleukin-33 receptor complex (IL-33R)

The Interleukin-33 (IL-33) receptor complex is a heterodimeric signaling unit composed of the primary binding subunit ST2 (also known as IL1RL1) and the co-receptor Interleukin-1 receptor accessory protein (IL-1RAcP) (UniProt: Q01638, Q9NPH3). Upon binding of the alarmin cytokine IL-33 to ST2, the complex recruits IL-1RAcP to initiate intracellular signaling pathways, including NF-κB and MAP kinases, which are critical for the activation of Th2 cells, mast cells, and group 2 innate lymphoid cells (ILC2s) (PMID: 25935015). This signaling axis plays a pivotal role in type 2 immunity and is heavily implicated in the pathogenesis of allergic and inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and atopic dermatitis (PMID: 30243714). Beyond inflammation, the IL-33/ST2 axis is involved in cardiac stress responses, where a soluble form of ST2 (sST2) acts as a decoy receptor and serves as a prognostic biomarker for heart failure (PMID: 21459245). Therapeutic strategies targeting this complex primarily involve monoclonal antibodies that block ST2 or IL-33, aiming to dampen the overactive immune responses seen in chronic respiratory and skin conditions. Clinical trials for these agents, such as astegolimab and itepekimab, have shown promise in reducing exacerbations and improving lung function in specific patient populations (PMID: 33503341).

Other names

ST2IL1RL1Interleukin 1 receptor-like 1IL-1R4T1/ST2DER4FIT-1

Monoclonal antibody antagonist that blocks the interaction between IL-33 and the ST2 subunit of the receptor complex, thereby inhibiting downstream pro-inflammatory signaling.