The DIC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells
The DIC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells
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DOI：
10.1182/blood-2006-09-048058
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发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Corbi, Angel L.
中科院分区：
文献类型：
--
作者：
Dominguez-Soto, Angeles;Aragoneses-Fenoll, Laura;Corbi, Angel L.
肝脏和淋巴结窦内皮细胞C型凝集素（LSEC tin [CLEC 4G]）是一种C型凝集素，编码于肝脏/淋巴结特异性细胞间粘附分子-3-抓取非整联蛋白（L-SIGN）/树突状细胞特异性细胞间粘附分子-3-抓取非整联蛋白（DC-SIGN）/CD 23基因簇中。LSECtin的表达以前被描述为局限于肝和淋巴结的窦状内皮细胞。我们现在报告LSECtin在人外周血和胸腺树突状细胞中的表达。在单核细胞衍生的巨噬细胞和树突细胞中也在RNA和蛋白质水平检测到LSECtin。在体外，白细胞介素-4（IL-4）诱导3种LSECtin选择性剪接亚型的表达，包括潜在可溶形式（Delta 2亚型）和原型分子的较短版本（Delta 3/4亚型）。LSECtin作为病原体受体发挥作用，因为它的表达赋予埃博拉病毒与白血病细胞结合的能力。糖结合研究表明，LSECtin特异性识别N-乙酰葡糖胺，而没有观察到LSECtin结合甘露聚糖或N-乙酰半乳糖胺。抗体或配体介导的接合触发LSECtin的快速内化，其依赖于细胞质tall内的含酪氨酸和二谷氨酸基序。因此，LSECtin是人骨髓细胞中的病原体相关分子模式受体。此外，我们的研究结果表明，LSECtin参与抗原摄取和内化，并可能是一个合适的靶分子在疫苗接种策略。
Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin [CLEC4G]) is a C-type lectin encoded within the liver/lymph node-specific intercellular adhesion molecule-3-grabbing nonintegrin (L-SIGN)/dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23 gene cluster. LSECtin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. We now report LSECtin expression in human peripheral blood and thymic dendritic cells isolated ex vivo. LSECtin is also detected in monocyte-derived macrophages and dendritic cells at the RNA and protein level. In vitro, interleukin-4 (IL-4) induces the expression of 3 LSECtin alternatively spliced isoforms, including a potentially soluble form (Delta 2 isoform) and a shorter version of the prototypic molecule (Delta 3/4 isoform). LSECtin functions as a pathogen receptor, because its expression confers Ebola virus-binding capacity to leukemic cells. Sugar-binding studies indicate that LSECtin specifically recognizes N-acetylglucosamine, whereas no LSECtin binding to Mannan- or N-acetyl-galactosaminecontaining matrices are observed. Anti- body or ligand-mediated engagement triggers a rapid internalization of LSECtin, which is dependent on tyrosine and diglutamic-containing motifs within the cytoplasmic tall. Therefore, LSECtin is a pathogen-associated molecular pattern receptor in human myeloid cells. In addition, our results suggest that LSECtin participates in antigen uptake and internalization, and might be a suitable target molecule in vaccination strategies.