Leukocyte‐associated immunoglobulin‐like receptor (LAIR)‐2 is a soluble competitor of the collagen/LAIR‐1 inhibitory immune interaction

Abstract

Leukocyte‐associated Ig‐like receptor (LAIR)‐1 is a collagen‐receptor that inhibits immune cell function upon collagen binding (Lebbink et al, J Exp Med, 2006). Next to LAIR‐1, the human genome encodes LAIR‐2, a putative soluble homologue. We now show that the LAIR‐2 gene is broadly transcribed in human peripheral blood mononuclear cells, mirroring the expression profile of LAIR‐1. LAIR‐2 protein is expressed as a soluble receptor exhibiting high affinity for various collagen molecules to which it binds in a hydroxyproline‐dependent manner. In vitro stimulation of peripheral blood mononuclear cells induces secretion of LAIR‐2. Interestingly, high amounts of LAIR‐2 are detected in urine of pregnant women, indicating that the soluble receptor is indeed produced in vivo and can be cleared from the body via urine. Furthermore, LAIR‐2 levels are increased in synovial fluid of patients with rheumatoid arthritis as compared to osteoarthritis patients. We hypothesize that soluble LAIR‐2 may function as a natural competitor for LAIR‐1, thereby regulating its inhibitory potential. Indeed, LAIR‐2 prevents binding of human LAIR‐1 to collagens and LAIR‐1 crosslinking in vitro, revealing a novel mechanism of immune regulation by a soluble LAIR receptor regulating the inhibitory potential of the membrane‐bound LAIR‐1 via competition for ligands.Supported by the Netherlands Organization for Scientific Research (NWO)