Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2)

Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) is a soluble member of the immunoglobulin superfamily expressed primarily in humans. Unlike its homolog LAIR1, which is a membrane-bound inhibitory receptor on immune cells, LAIR2 is secreted and acts as a natural decoy receptor in the extracellular environment[2][3][9]. LAIR2 binds to collagen and collagen-like molecules in the extracellular matrix with even higher affinity than LAIR1, competitively inhibiting LAIR1’s ability to suppress immune cell activation[2][3][4]. By blocking LAIR1-mediated inhibitory signaling, LAIR2 helps to modulate immune responses, playing a regulatory role in contexts such as cancer, infections, inflammation, and autoimmune diseases. Overexpression or therapeutic administration of LAIR2, such as through engineered fusion proteins like NC410, is being explored as a strategy to reverse tumor-induced immune suppression and enhance anti-tumor immunity[2][4][3]. LAIR2 is present in bodily fluids (e.g., blood, synovial fluid, urine), and its expression is regulated by immune activation and inflammatory signals[2][3][4].

Other names

LAIR2LAIR-2CD306leukocyte-associated Ig-like receptor-2

Functions as a decoy receptor by binding collagens in the extracellular matrix with high affinity, thereby competitively inhibiting the binding of these ligands to membrane-bound inhibitory receptor LAIR-1, which restores or enhances immune cell activation. NC410 and similar fusion proteins use this decoy function to block LAIR-1 inhibitory signaling in the tumor microenvironment, reversing immune suppression and promoting antitumor immunity.