Interleukin-33 receptor (ST2) (ST2)

Interleukin‑33 receptor (ST2), also known as interleukin‑1 receptor-like 1 (IL1RL1), is a member of the interleukin 1 receptor family within the immunoglobulin superfamily. It exists in two main forms generated by alternative splicing: a membrane-bound form that mediates signal transduction upon binding its ligand interleukin‑33 (IL‑33), and a soluble form that acts as a decoy by sequestering free IL‑33 without initiating signaling. The membrane-bound ST2 forms a heterodimeric complex with the interleukin 1 accessory protein (IL‑1RAcP) after binding IL–33, leading to recruitment of MyD88 adaptor protein and activation of downstream pathways including NF–κB and MAP kinases. This results in production of Th₂-associated cytokines such as IL–4, IL–5, and IL–13. ST₂ is expressed on various immune cells including Th₂ cells, regulatory T cells, group ２ innate lymphoid cells, mast cells, eosinophils, basophils—as well as some CNS-resident cell types like astrocytes and neurons. The ST２/IL–３３ axis plays critical roles in regulating inflammation—promoting type II immune responses—and has been implicated in allergic diseases such as asthma; it also modulates neuroinflammation following CNS injury or stroke by influencing microglial activity. Soluble ST２ serves both physiological regulatory functions—by limiting excessive signaling—and clinical utility—as an established biomarker for heart failure prognosis due to its association with cardiac stress. Therapeutic strategies targeting this pathway include monoclonal antibodies against either ST２ or its ligand; these approaches aim to dampen pathological inflammation but must balance potential risks related to impaired host defense or tissue repair processes

Other names

IL-33 receptorIL1RL1Interleukin-1 receptor-like 1IL-33RT1/ST2

For drugs targeting this molecule, mechanisms include blockade of ligand-receptor interaction to inhibit downstream signaling pathways such as NF‑κB and MAP kinase activation, or use of soluble ST2 as a decoy to sequester IL‑33