decoyreceptor

Decoy receptors are receptors that bind their ligands but do not initiate the conventional signal transduction that follows receptor engagement. By capturing ligands, they reduce the availability of the ligand to signaling receptors and thus modulate cellular responses. Decoy receptors can be membrane-bound, residing on the cell surface, or soluble, circulating in body fluids after proteolytic shedding or alternative splicing. They can dampen or redirect signaling across cytokine, growth factor, apoptotic, and angiogenic pathways.

Membrane-bound and soluble forms expand the regulatory options for the cell. In physiology, decoy receptors help fine-tune immune responses, bone remodeling, and tissue vascularization by limiting excessive or inappropriate signaling. They may also participate in pathological states, such as cancer, inflammation, and autoimmune diseases, where ligand availability shapes disease progression or response to therapy.

Prominent examples include interleukin-1 receptor type II (IL-1RII), which binds IL-1α and IL-1β but lacks a functional signaling domain, thereby reducing IL-1 activity. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL and, to some extent, for TRAIL, influencing osteoclastogenesis and bone turnover. DcR3 (TRAIL decoy receptor 3) binds Fas ligand, LIGHT, and TL1A, modulating immune signaling and tumor immunity. The TRAIL receptors DcR1 (TRAIL-R3) and DcR2 (TRAIL-R4) are membrane-bound decoys for TRAIL that do not transmit apoptosis. Soluble VEGF receptor-1 (sFlt-1) acts as a decoy for VEGF, impacting angiogenesis.

Decoy receptors are of interest therapeutically as receptor traps to neutralize specific ligands in diseases characterized by excessive or pathogenic signaling.