The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction
Lebbink, R.J.; van den Berg, M.C.; de Ruiter, T.; Raynal, N.; van Roon, J.A.G.; Lenting, P.J.; Jin, B.; Meyaard, L.
(2008) Journal of Immunology, volume 180, issue 3, pp. 1662 - 1669
(Article)
Abstract
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
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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.
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Keywords: Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, Binding, Competitive, Cell Line, Collagen, Female, Humans, Immunity, Leukocytes, Mononuclear, Ligands, Male, Middle Aged, Pregnancy, Receptors, Immunologic, Synovial Fluid, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0022-1767
Publisher: American Association of Immunologists
(Peer reviewed)
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