Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response.
Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response.
复制标题
DOI：
10.1053/j.gastro.2009.07.051
复制
发表时间：
2009-10
期刊：
影响因子：
29.4
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Tang L;Yang J;Liu W;Tang X;Chen J;Zhao D;Wang M;Xu F;Lu Y;Liu B;Sun Q;Zhang L;He F
肝脏是一个具有矛盾免疫特性的器官，并以其耐受性微环境而闻名，这对肝脏疾病具有重要意义。然而，这种局部免疫抑制的分子基础却知之甚少。在这项研究中，我们的目的是确定肝窦内皮细胞凝集素（LSECtin），最近确定的树突状细胞特异性ICAM-3抓取非整合素（DC-SIGN）家族的成员，在调节肝脏T细胞免疫应答的作用。通过抗CD 3/CD 28单克隆抗体和LSECtin蛋白共刺激T细胞或T细胞受体转基因T细胞与小鼠LSECs体外共培养来确定LSECtin对T细胞效应功能的调节。我们建立了LSECtin基因敲除小鼠模型，制备了重组LSECtin蛋白和互补DNA质粒，以分析LSECtin在体内肝脏T细胞免疫调节中的作用。我们发现LSECtin特异性识别活化的T细胞并负调节其免疫应答。在患有T细胞介导的急性肝损伤的小鼠中，由于增加的T细胞免疫应答，LSECtin的缺乏加速了疾病，而外源性施用重组LSECtin蛋白或质粒通过下调T细胞免疫来改善疾病。我们的研究结果表明，LSECtin是一种新型的T细胞调节因子，揭示了肝脏T细胞免疫抑制的关键机制，可能为肝脏炎症性疾病的治疗开辟了新的途径。
The liver is an organ with paradoxic immunologic properties and is known for its tolerant microenvironment, which holds important implications for hepatic diseases. The molecular basis for this local immune suppression, however, is poorly understood. In this study, we aimed to determine the role of liver sinusoidal endothelial cell lectin (LSECtin), a recently identified member of the dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) family, in the regulation of hepatic T-cell immune response. The regulation of T-cell effector function by LSECtin was determined by co-stimulated T cells with anti-CD3/CD28 monoclonal antibody and LSECtin protein, or co-culture of T-cell receptor transgenic T cells with mouse LSECs in vitro. We generated LSECtin knockout mice and prepared recombinant LSECtin protein and complementary DNA plasmids to analyze the role of LSECtin in hepatic T-cell immune regulation in vivo. We showed that LSECtin specifically recognized activated T cells and negatively regulated their immune responses. In mice with T-cell–mediated acute liver injury, the lack of LSECtin accelerated the disease owing to an increased T-cell immune response, whereas the exogenous administration of recombinant LSECtin protein or plasmid ameliorated the disease via down-regulation of T-cell immunity. Our results reveal that LSECtin is a novel regulator of T cells and expose a crucial mechanism for hepatic T-cell immune suppression, perhaps opening up a new approach for treatment of inflammatory diseases in the liver.
登录
查看更多内容
影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
影响因子：
15.9
作者：
TIEGS, G;HENTSCHEL, J;WENDEL, A
通讯作者：
WENDEL, A
影响因子：
13.5
作者：
Spangenberg, HC;Viazov, S;Thimme, R
通讯作者：
Thimme, R
影响因子：
13.5
作者：
Dominguez-Soto, Angeles;Aragoneses-Fenoll, Laura;Corbi, Angel L.
通讯作者：
Corbi, Angel L.