Sphingosine-1 phosphate signaling regulates positioning of dendritic cells within the spleen
Sphingosine-1 phosphate signaling regulates positioning of dendritic cells within the spleen
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DOI：
10.4049/jimmunol.179.9.5855
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Foerster, Reinhold
中科院分区：
文献类型：
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作者：
Czeloth, Niklas;Schippers, Angela;Foerster, Reinhold
获得性免疫反应的成功执行和平衡需要控制树突状细胞(DC)进入和导航到次级淋巴器官和内部。尽管DC从外周非淋巴器官迁移到其引流淋巴结的机制已被发现，但对控制脾或淋巴结内DC正确定位的分子线索知之甚少。在这项研究中，我们证明了神经鞘氨醇-1磷酸(SIP)受体1影响未成熟DC在小鼠脾内的定位。在用FTY720或SEW2871这两种已知干扰SIP1介导的信号传导的药物治疗后，33D1(+)DC亚群从桥接通道均匀地重新分布到边缘区域。相反，CD205(+)DC亚群仍然与T细胞区相关。体内处理后，成熟的DC聚集在T细胞区。在没有CCR7的情况下，脂多糖驱动的再分配发生，FTY720不能阻止，这表明未成熟和成熟的DC的引导机制不同。结合观察到的DC亚型特异性的SIP受体的表达模式，以及伴随着DC成熟而导致的SIP1和SIP2的显著上调，这些结果表明，SIP2信号在DC在脾内的运动和迁移中起决定性作用。
A successful execution and balance of adaptive immune responses requires a controlled positioning and navigation of dendritic cells (DC) into and inside secondary lymphoid organs. Whereas mechanisms were identified governing the migration of DC from peripheral nonlymphoid organs into their draining lymph nodes, little is known about the molecular cues controlling the proper positioning of spleen or lymph node resident DC. In this study, we show that the sphingosine-1 phosphate (SIP) receptor 1 influences the positioning of immature DC inside the murine spleen. Following treatment with FTY720 or SEW2871, drugs known to interfere with SIP1-mediated signaling, the 33D1(+) DC subpopulation homogeneously redistributes from the bridging channels to the marginal zone. In contrast, the CD205(+) DC subset remains associated with the T cell zone. Upon in vivo LPS treatment, the maturing DC assemble in the T cell zone. The LPS-driven redistribution occurs in the absence of CCR7 and cannot be prevented by FTY720, indicating that guiding mechanisms differ between immature and mature DC. Along with the observed DC subtype-specific SIP receptor expression pattern as well as the profound up-regulation of SIP, and SIP, accompanying DC maturation, these results suggest a decisive contribution of SIP signaling to intrasplenic DC motility and migration.