Interleukin-1 receptor type 2 (IL-1R2)

Interleukin-1 receptor type 2 (IL-1R2), also known as CD121b, is a non-signaling decoy receptor that belongs to the interleukin-1 receptor family (UniProt, Wikipedia). Unlike the type 1 receptor (IL-1R1), IL-1R2 lacks a signaling Toll-IL-1 receptor (TIR) domain, allowing it to bind IL-1 ligands (IL-1α and IL-1β) and the co-receptor IL-1RAP without initiating a pro-inflammatory cascade (PubMed, IUPHAR). This sequestration effectively neutralizes IL-1 activity, making IL-1R2 a critical negative regulator of inflammation (Science, J Exp Med). In disease states, IL-1R2 is often dysregulated; it is upregulated in sepsis and certain cancers, where it may contribute to immune evasion by suppressing anti-tumor responses, particularly when expressed on regulatory T cells (Tregs) (Frontiers, eScholarship). Conversely, its downregulation is associated with chronic inflammatory conditions like atherosclerosis (BBA - Molecular and Cell Biology of Lipids). Therapeutically, IL-1R2 is being explored as a biomarker for inflammatory severity and as a target for monoclonal antibodies in cancer immunotherapy to modulate the tumor microenvironment (PubMed, ResearchGate). Glucocorticoids like dexamethasone and cytokines such as IL-4 are known to induce its expression, contributing to their anti-inflammatory effects (Science, J Exp Med).

Other names

CD121bIL1R2IL1RBCDw121bIL-1R-2IL-1RT-2IL-1RT2Interleukin-1 receptor betaCD121 antigen-like family member BInterleukin-1 receptor type II

Decoy receptor mechanism: binds IL-1 ligands (IL-1α, IL-1β) and the co-receptor IL-1 receptor accessory protein (IL-1RAP) without initiating signal transduction, thereby preventing the formation of the active IL-1R1/IL-1RAP signaling complex.