Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.
Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.
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DOI：
10.1093/intimm/dxh093
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发表时间：
2004-07
影响因子：
4.4
通讯作者：
H. Yoneyama;K. Matsuno;Yanyun Zhang;T. Nishiwaki;M. Kitabatake;S. Ueha;S. Narumi;S. Morikawa
中科院分区：
文献类型：
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作者：
H. Yoneyama;K. Matsuno;Yanyun Zhang;T. Nishiwaki;M. Kitabatake;S. Ueha;S. Narumi;S. Morikawa
树突状细胞(DC)募集到淋巴结(LNS)是建立免疫应答的关键。尽管DC已被证实通过传入淋巴途径从外周组织进入LNS，但DCs是否也从循环直接迁移到LNS仍是一个问题。在这里，我们证明了血浆细胞样树突状细胞(PDC)前体可以在小鼠炎症的LNS的高内皮微静脉(HEV)中迁移。细菌感染可诱导大量PDC和髓系DC前体细胞进入血液循环。除CXCR3外，这两个亚群都表达一组共同的趋化因子受体，表现为平行动员进入血液，但显示出不同的向LNS的运输途径。在短期归巢试验中，MDC前体迁移到外周组织并随后引流LNS，而PDC前体以CXCL9和E-选择素依赖的方式直接进入LNS。肿瘤坏死因子-α不仅控制DC前体向血液中的动员，而且还控制LN HEV上趋化因子的上调。在病毒感染中也观察到了类似的转运途径，CXCR3(-/-)小鼠来源的PDC前体显示出缺陷的跨HEV迁移。这项研究阐明了DC前体运输的炎症依赖、趋化因子驱动的独特性质。
Recruitment of dendritic cells (DCs) to lymph nodes (LNs) is pivotal to the establishment of immune response. Whereas DCs have been proven to undergo afferent lymphatic pathway to enter LNs from peripheral tissues, a question remains if DCs also migrate into LNs directly from the circulation. Here we demonstrate that plasmacytoid DC (pDC) precursors can transmigrate across high endothelial venules (HEVs) of inflamed LNs in mice. Bacterial infection induces a significant number of pDC and myeloid DC (mDC) precursors into the circulation. Both subsets express a common set of chemokine receptors except CXCR3, display parallel mobilization into the blood, but show distinct trafficking pathway to the LNs. In a short-term homing assay, whereas mDC precursors migrate to peripheral tissues and subsequently to draining LNs, pDC precursors directly enter the LNs in a CXCL9 and E-selectin dependent manner. Tumor necrosis factor-alpha controls not only DC precursor mobilization into the blood but also chemokine up-regulation on LN HEVs. A similar trafficking pathway is observed also in viral infection, and CXCR3(-/-) mice-derived pDC precursors show defective trans-HEV migration. This study clarifies the inflammation-dependent, chemokine-driven distinct property of DC precursor trafficking.