Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels
Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels
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DOI：
10.1016/j.celrep.2016.01.048
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发表时间：
2016-02-23
期刊：
影响因子：
8.8
通讯作者：
Halin, Cornelia
中科院分区：
文献类型：
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作者：
Russo, Erica;Teijeira, Alvaro;Halin, Cornelia
为了诱导适应性免疫，树突状细胞（DC）通过传入淋巴管（LV）迁移到引流淋巴结（dLN）。这个过程分几个连续的步骤进行。在进入毛细淋巴管后，DC首先主动爬入下游集合管。从那里，它们接下来通过淋巴液流动被动和快速地转运到dLN。在这里，我们描述了趋化因子CCL 21在淋巴内DC爬行中的作用。在小鼠皮肤中进行延时成像，我们发现，阻断CCL 21-但不是淋巴流的缺乏-完全废除DC从毛细血管向集合血管的迁移，并降低了淋巴内DC从皮肤中迁移的能力。此外，我们发现，在体外低层流建立了一个CCL 21梯度沿着淋巴管内皮细胞单层，从而诱导下游定向DC迁移。这些发现揭示了淋巴内CCL 21通过形成流动诱导的梯度在促进DC向dLN运输中的作用。
To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient.