The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the Collagen/LAIR-1 inhibitory immune interaction
The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the Collagen/LAIR-1 inhibitory immune interaction
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DOI：
10.4049/jimmunol.180.3.1662
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Meyaard, Linde
中科院分区：
文献类型：
--
作者：
Lebbink, Robert Jan;van den Berg, Maaike C. W.;Meyaard, Linde
白细胞相关Ig样受体（LAIR）-1是一种胶原蛋白受体，在胶原蛋白结合时抑制免疫细胞功能。在LAIR-1之后，人类基因组编码LAIR-2，一种推定的可溶性同源物。在这项研究中，我们首次发现，LAIR-2基因在人PBMC中广泛转录，反映了LAIR-1的表达谱。LAIR-2蛋白表达为可溶性受体，其对各种胶原分子表现出高亲和力，其以羟脯氨酸依赖性方式与胶原分子结合。PBMC的体外刺激诱导LAIR-2的分泌。我们在孕妇的尿液中检测到大量的LAIR-2，表明可溶性受体确实在体内产生，并且可以通过尿液从体内清除。此外，与骨关节炎患者相比，类风湿性关节炎患者滑液中的LAIR-2水平增加。我们推测可溶性LAIR-2可能作为LAIR-1的天然竞争者发挥作用，从而调节其抑制潜力。事实上，LAIR-2在体外阻止人LAIR-1与胶原的结合和LAIR-1交联，表明该蛋白在体内具有免疫调节功能。因此，我们揭示了一种新的免疫调节机制的可溶性LAIR受体调节抑制潜力的膜结合LAIR-1通过竞争配体。
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.