Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals
Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals
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DOI：
10.1073/pnas.0607285104
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发表时间：
2007-04-03
影响因子：
11.1
通讯作者：
Platt, Frances M.
中科院分区：
文献类型：
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作者：
Speak, Anneliese O.;Salio, Mariolina;Platt, Frances M.
恒定自然杀伤T（iNKT）细胞的发育需要胸腺中CD1d分子呈递脂质配体。已提出鞘糖脂（GSL）异葡萄糖三己糖神经酰胺（iGb3）作为胸腺中的天然iNKT细胞选择配体，并参与树突状细胞（DC）对iNKT细胞的外周活化。然而，在小鼠或人胸腺或DC中没有iGb3存在的直接生物化学证据。使用高度灵敏的HPLC测定，在小鼠中可以检测到iGb3的唯一组织是背根神经节（DRG）。在所分析的其他小鼠或任何人组织（包括胸腺和DC）中未检测到iGb3。即使在背根节中储存了同种异体GSL的突变小鼠中，我们仍然无法在胸腺中检测到这些GSL。因此，iGb3不太可能是小鼠和人类中生理学相关的iNKT细胞选择配体。现在有必要进行详细的研究，以更好地了解iNKT细胞选择配体在体内的性质。
Development of invariant natural killer T (iNKT) cells requires the presentation of lipid ligand(s) by CD1d molecules in the thymus. The glycosphingolipid (GSL) isoglobotrihexosylceramide (iGb3) has been proposed as the natural iNKT cell-selecting ligand in the thymus and to be involved in peripheral activation of iNKT cells by dendritic cells (DCs). However, there is no direct biochemical evidence for the presence of iGb3 in mouse or human thymus or DCs. Using a highly sensitive HPLC assay, the only tissue where iGb3 could be detected in mouse was the dorsal root ganglion (DRG). iGb3 was not detected in other mouse or any human tissues analyzed, including thymus and DCs. Even in mutant mice that store isoglobo-series GSLs in the DRG, we were still unable to detect these GSLs in the thymus. iGb3 is therefore unlikely to be a physiologically relevant iNKT cell-selecting ligand in mouse and humans. A detailed study is now warranted to better understand the nature of iNKT cell-selecting ligand(s) in vivo.