Dendritic cell migration to the T-cell-rich areas of the lymph node is essential for their ability to initiate the adaptive immune response. While it has been shown that the actin cytoskeleton is required for normal DC migration, the role of many of the individual cytoskeletal molecules is poorly understood. In this study, we investigated the contribution of the Arp2/3 complex binding protein, haematopoietic lineage cell-specific protein 1 (HS1), to DC migration and force generation. We quantified the random migration of HS1^−/− DCs on 2D micro-contact printed surfaces and found that in the absence of HS1, DCs have greatly reduced motility and speed. This same reduction in motility was recapitulated when adding Arp2/3 complex inhibitor to WT DCs or using DCs deficient in WASP, an activator of Arp2/3 complex-dependent actin polymerization. We further investigated the importance of HS1 by measuring the traction forces of HS1^−/− DCs on micropost array detectors (mPADs). In HS1 deficient DCs, there was a significant reduction in force generation (3.96 ± 0.40 nN per cell) compared to WT DCs (13.76 ± 0.84 nN per cell). Interestingly, the forces generated in DCs lacking WASP were only slightly reduced compared to WT DCs. Taken together, these findings show that HS1 and Arp2/3 complex-mediated actin polymerization are essential for the most efficient DC random migration and force generation.

中文翻译：

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Arp2 / 3复合物结合蛋白HS1是有效的树突状细胞随机迁移和产生力所必需的

树突状细胞向淋巴结的T细胞富集区域的迁移对于它们启动适应性免疫反应的能力至关重要。虽然已经表明正常直流迁移需要肌动蛋白细胞骨架，但许多单个细胞骨架分子的作用却知之甚少。在这项研究中，我们调查了Arp2 / 3复合物结合蛋白，造血谱系细胞特异性蛋白1（HS1）对DC迁移和产生力的贡献。我们量化了HS1 ^-/-的随机迁移二维微接触印刷表面上的DC，发现在没有HS1的情况下，DC的运动性和速度大大降低。当向WT DC中添加Arp2 / 3复合抑制剂或使用缺乏WASP的DC（Arp2 / 3与复合物相关的肌动蛋白聚合反应的活化剂）时，同样会降低运动性。我们通过测量HS1 ^-/-的牵引力进一步研究了HS1的重要性微柱阵列检测器（mPAD）上的DC。与WT DC（每个单元13.76±0.84 nN）相比，在缺乏HS1的DC中，力的产生显着减少（每个单元3.96±0.40 nN）。有趣的是，与WT DC相比，缺少WASP的DC中产生的力仅略有降低。综上所述，这些发现表明，HS1和Arp2 / 3复合物介导的肌动蛋白聚合对于最有效的DC随机迁移和力产生至关重要。