The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction.
Leukocyte-associated Ig-like receptor (LAIR)-1 is a collagen-receptor that inhibits immune cell function upon collagen binding. Next to LAIR-1, the human genome encodes LAIR-2, a putative soluble homolog. In this study we show, for the first time, that the LAIR-2 gene is broadly transcribed in human PBMC, 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 PBMC induces secretion of LAIR-2. We detect high amounts of LAIR-2 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 with 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 cross-linking in vitro, suggesting that the protein has an immunoregulatory function in vivo. Hence, we reveal 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.
Lebbink
Robert Jan
RJ
Department of Immunology, University Medical Center Utrecht, Lundlaan 6, Utrecht, The Netherlands.
van den Berg
Maaike C W
MC
de Ruiter
Talitha
T
Raynal
Nicolas
N
van Roon
Joel A G
JA
Lenting
Peter J
PJ
Jin
Boquan
B
Meyaard
Linde
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001667:Binding, Competitive; D002460:Cell Line; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007109:Immunity; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013582:Synovial Fluid / Q000276:immunology
C431503:LAIR-2 receptor; D008024:Ligands; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; D003094:Collagen