PDF(Pubmed)
Abstract：
Migrating cells preferentially breach and integrate epithelial and endothelial monolayers at multicellular vertices. These sites are amenable to forces produced by the migrating cell and subsequent opening of the junctions. However, the cues that guide migrating cells to these entry portals, and eventually drive the transmigration process, are poorly understood. Here, we show that lymphatic endothelium multicellular junctions are the preferred sites of dendritic cell transmigration in both primary cell co-cultures and in mouse dermal explants. Dendritic cell guidance to multicellular junctions was dependent on the dendritic cell receptor CCR7, whose ligand, lymphatic endothelial chemokine CCL21, was exocytosed at multicellular junctions. Characterization of lymphatic endothelial secretory routes indicated Golgi-derived RAB6+ vesicles and RAB3+/27+ dense core secretory granules as intracellular CCL21 storage vesicles. Of these, RAB6+ vesicles trafficked CCL21 to the multicellular junctions, which were enriched with RAB6 docking factor ELKS (ERC1). Importantly, inhibition of RAB6 vesicle exocytosis attenuated dendritic cell transmigration. These data exemplify how spatially-restricted exocytosis of guidance cues helps to determine where dendritic cells transmigrate.
摘要：
迁移细胞优先在多细胞顶点处破坏并整合上皮和内皮单层。这些位点适合于由迁移细胞和随后的连接开口产生的力。然而,引导细胞迁移到这些入口的线索，并最终推动了迁移过程，知之甚少。这里,我们表明，在原代细胞共培养和小鼠真皮外植体中，淋巴管内皮多细胞连接是树突状细胞迁移的首选位点。树突状细胞对多细胞连接的引导依赖于树突状细胞受体CCR7,淋巴管内皮趋化因子CCL21在多细胞连接处胞吐。淋巴内皮分泌途径的表征表明高尔基体衍生的RAB6囊泡和RAB3/27致密核心分泌颗粒作为细胞内CCL21储存囊泡。其中,RAB6+囊泡运输CCL21到多细胞连接，用RAB6对接因子ELKS（ERC1）富集。重要的是,抑制RAB6囊泡的胞吐作用减弱了树突状细胞的迁移。这些数据举例说明了引导线索的空间限制性胞吐作用如何有助于确定树突状细胞的迁移位置。
