3-O-sulfo-β-d-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5
3-O-sulfo-β-d-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5
复制标题
内源性磺基糖脂的 3-O-磺基-β-d-半乳糖部分是免疫球蛋白样受体 LMIR5 的潜在配体
DOI：
10.1016/j.molimm.2014.07.023
复制
发表时间：
2015
影响因子：
3.6
通讯作者：
Yamasaki S
中科院分区：
文献类型：
--
作者：
Phongsisay V;Iizasa E;Hara H;Yamasaki S
轴突格林-巴勒综合征（GBS）是一种自身免疫性神经病变，其特征是由于存在针对脑糖脂的自身抗体而导致肢体无力和/或瘫痪。识别这些自身免疫靶标的免疫受体尚未被描述。本研究从脑糖脂中筛选了12种c型凝集素和10种免疫球蛋白样受体的潜在配体，这些配体是GBS自身抗体的结合靶点。这些糖脂分别是GM1、GM2、GD1a、GD1b、GQ1b、粗神经节苷脂和3- o-磺基-β-d-半乳糖神经酰胺C24:1（简称C24:1）。配体和受体之间的直接相互作用是通过elisa结合试验来检测的。c型凝集素（CLEC5a, SIGNR3）和免疫球蛋白样受体（TREM2, TREM3, LMIR2, LMIR5, LMIR7, LMIR8）与C24:1相互作用。此外，TREM3确实与GQ1b结合。LMIR5与GD1a、GQ1b和粗神经节苷相互作用。观察到LMIR5-C24:1相互作用具有最高亲和力的结合，选择该相互作用进行进一步验证。发现C24:1在嗜碱性细胞中诱导MCP-1的产生，而不是促炎细胞因子。c24:1诱导的MCP-1在DAP12−/−嗜碱性细胞中显著减少。重要的是，C24:1连接LMIR5导致表达LMIR5的报告细胞通过DAP12激活NFAT。结构分析表明LMIR5识别C24:1的3- o-磺基-β-d-半乳糖片段。这些发现表明C24:1是dap12偶联LMIR5的潜在配体。
Axonal Guillain–Barré syndrome (GBS) is an autoimmune neuropathy characterized by limb weakness and/or paralysis due to the presence of autoantibodies against brain glycolipids. The immune receptors that recognize these autoimmune targets have not been described. In this study, 12 C-type lectin and 10 immunoglobulin-like receptors were screened for their potential ligands from the brain glycolipids, which are the binding targets for GBS autoantibodies. These glycolipids were GM1, GM2, GD1a, GD1b, GQ1b, crude gangliosides, and 3-O-sulfo-β-d-galactosylceramide C24:1 (designated as C24:1). A direct interaction between ligand and receptor was examined using an ELISA-based binding assay. C-type lectin (CLEC5a, SIGNR3) and immunoglobulin-like receptors (TREM2, TREM3, LMIR2, LMIR5, LMIR7, LMIR8) interacted with C24:1. In addition, TREM3 did bind to GQ1b. LMIR5 interacted with GD1a, GQ1b, and crude gangliosides. Binding with highest affinity was observed for the LMIR5–C24:1 interaction, which was selected for further verification. C24:1 was found to induce MCP-1 production, but not proinflammatory cytokines, in basophils. C24:1-induced MCP-1 production was significantly reduced in DAP12−/−basophils. Importantly, LMIR5 ligation by C24:1 resulted in NFAT activation through DAP12 in LMIR5-expressing reporter cells. Structural analysis showed that LMIR5 recognized the 3-O-sulfo-β-d-galactose moiety of C24:1. The findings indicated that C24:1 is a potential ligand for DAP12-coupled LMIR5.