IL1R1

IL1R1, or interleukin-1 receptor type 1, is a transmembrane receptor that binds the pro-inflammatory cytokines IL-1α and IL-1β. It is a central component of the innate immune system and plays a key role in initiating inflammatory responses to infection and tissue injury. Ligand binding to IL-1R1 activates signaling cascades that promote the expression of inflammatory genes and mediators.

The receptor belongs to the IL-1 receptor/Toll-like receptor superfamily. Its extracellular portion contains three immunoglobulin-like domains that recognize IL-1α and IL-1β. The intracellular region contains a Toll/IL-1 receptor (TIR) domain that propagates signal after ligand binding. For signaling to occur, IL-1R1 must form a complex with the IL-1 receptor accessory protein (IL-1RAcP). This ternary complex recruits adaptor proteins such as MyD88 and kinases like IRAK4 and IRAK1, leading to activation of downstream pathways including NF-κB and MAPKs and the production of inflammatory mediators such as IL-6, IL-8, and TNF.

IL-1R1 is broadly expressed on many cell types including myeloid cells, endothelial cells, and fibroblasts. In addition to the membrane-bound receptor, soluble forms can act as decoys to modulate signaling. Regulation of IL-1R1 signaling is further affected by decoy receptors (such as IL-1R2) and natural antagonists (like IL-1 receptor antagonist, IL-1Ra).

Dysregulation of IL-1R1 signaling is implicated in autoinflammatory and autoimmune diseases, sepsis, and chronic inflammatory conditions. Therapeutically, IL-1R1 is targeted by agents such as anakinra (a recombinant IL-1Ra) that blocks receptor activation and dampens inflammation.