Migration of CD4 T cells and dendritic cells toward sphingosine 1-phosphate (SIP) is mediated by different receptor subtypes: S1P regulates the functions of murine mature dendritic cells via S1P receptor type 3
Migration of CD4 T cells and dendritic cells toward sphingosine 1-phosphate (SIP) is mediated by different receptor subtypes: S1P regulates the functions of murine mature dendritic cells via S1P receptor type 3
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DOI：
10.4049/jimmunol.178.6.3437
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Chiba, Kenji
中科院分区：
文献类型：
--
作者：
Maeda, Yasuhiro;Matsuyuki, Hirofumi;Chiba, Kenji
已知树突状细胞（DC）和淋巴细胞对磷脂介质鞘氨醇1-磷酸（SIP）显示迁移反应。然而，目前尚不清楚是否相同的SIP受体亚型介导的淋巴细胞和DC向S1 P的迁移。在这项研究中，我们研究了SIP受体亚型参与S1 P诱导的小鼠CD 4 T细胞和骨髓来源的DC迁移。0.1 nM或更高浓度的有效S1 P受体激动剂FTY 720-磷酸盐的（S）-对映体[（S）-FTY 720-P]和0.1 μ M或更高浓度的选择性1型SIP受体（S1 P（1））激动剂SEW 2871诱导SIP的剂量依赖性下调。用这些化合物预处理导致小鼠CD 4 T细胞向SIP迁移的显著抑制。因此，揭示了CD 4 T细胞向SIP的迁移高度依赖于SIP。成熟DCs较CD 4 T细胞和未成熟DCs表达更高水平的SIP mRNA。10-1000 nM的SIP诱导了显著的迁移，并显著增强了成熟但非未成熟DC中FITC-葡聚糖的内吞作用。用0.1 μ M或更高浓度的（S）-FTY 720-P预处理导致SIP诱导的成熟DC迁移和内吞作用的显著抑制，而高达100 μ M的SEW 2871没有显示出任何明显的作用。此外，我们发现SIP诱导的迁移和内吞作用在从S1 P（3）基因敲除小鼠制备的成熟DC中处于极低水平。这些结果表明，SIP通过S1 P（3）而不是S1 P（1）调节小鼠成熟DC的迁移和内吞作用。
Dendritic cells (DCs) and lymphocytes are known to show a migratory response to the phospholipid mediator, sphingosine 1-phosphate (SIP). However, it is unclear whether the same SIP receptor subtype mediates the migration of lymphocytes and DCs toward S1P. In this study, we investigated the involvement of SIP receptor subtypes in S1P-induced migration of CD4 T cells and bone marrow-derived DCs in mice. A potent S1P receptor agonist, the (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P], at 0.1 nM or higher and a selective SIP receptor type 1 (S1P(1)) agonist, SEW2871, at 0.1 mu M or higher induced a dose-dependent down-regulation of SIP,. The pretreatment with these compounds resulted in a significant inhibition of mouse CD4 T cell migration toward SIP. Thus, it is revealed that CD4 T cell migration toward SIP is highly dependent on SIP,. Mature DCs, when compared with CD4 T cells or immature DCs, expressed a relatively higher level of SIP, mRNA. SIP at 10-1000 nM induced a marked migration and significantly enhanced the endocytosis of FITC-dextran in mature but not immature DCs. Pretreatment with (S)-FTY720-P at 0.1 mu M or higher resulted in a significant inhibition of SIP-induced migration and endocytosis in mature DCs, whereas SEW2871 up to 100 mu M did not show any clear effect. Moreover, we found that SIP-induced migration and endocytosis were at an extremely low level in mature DCs prepared from S1P(3)-knockout mice. These results indicate that SIP regulates migration and endocytosis of murine mature DCs via S1P(3) but not S1P(1).