Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
IST Austria, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
Cell Rep. 2016 Feb 23;14(7):1723-1734. doi: 10.1016/j.celrep.2016.01.048. Epub 2016 Feb 11.
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.
为了诱导适应性免疫，树突状细胞（DC）通过输入淋巴管（LV）迁移到引流淋巴结（dLN）。这个过程发生在几个连续的步骤中。进入淋巴管后，DC 首先主动地向下游收集管爬行。从那里，它们被淋巴流被动而迅速地运送到 dLN。在这里，我们描述了趋化因子 CCL21 在淋巴管内 DC 爬行中的作用。在鼠皮中进行延时成像，我们发现阻断 CCL21-但不是没有淋巴流-完全阻止了 DC 从毛细血管向收集管的迁移，并降低了淋巴管内 DC 从皮肤中迁出的能力。此外，我们发现，体外低层流在淋巴管内皮单层上建立了 CCL21 梯度，从而诱导 DC 向下游迁移。这些发现揭示了淋巴管内 CCL21 在通过形成流动诱导的梯度促进 DC 向 dLN 迁移中的作用。
