Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1
Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1
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DOI：
10.1038/ni.3750
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发表时间：
2017-07-01
影响因子：
30.5
通讯作者：
Jackson, David G.
中科院分区：
文献类型：
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作者：
Johnson, Louise A.;Banerji, Suneale;Jackson, David G.
组织树突状细胞（DC）通过淋巴的运输对于引流淋巴结（LN）中细胞免疫应答的产生至关重要。在目前的研究中，我们发现DCs停靠在淋巴管的基底外侧表面，并通过透明质酸介导的与淋巴特异性内皮受体LYVE-1的相互作用，在动态transmigratory-cup-like结构中过渡到管腔。此外，我们发现Lyve 1基因的靶向缺失、抗体阻断或DC透明质酸涂层的消耗不仅延迟了真皮DC的淋巴运输，而且减弱了它们在皮肤引流淋巴结中引发CD 8（+）T细胞应答的能力。我们的研究结果揭示了LYVE-1以前未知的功能，并表明通过淋巴网络的运输是由白细胞衍生的透明质酸的识别启动的。
Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8(+) T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.