Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations
Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations
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DOI：
10.1016/j.immuni.2017.10.020
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发表时间：
2017-11-21
期刊：
影响因子：
32.4
通讯作者：
Meier-Schellersheim, Martin
中科院分区：
文献类型：
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作者：
Aronin, Caren E. Petrie;Zhao, Yun M.;Meier-Schellersheim, Martin
趋化因子介导的造血细胞募集到病原体生长或组织损伤的部位对宿主防御和器官动态平衡至关重要。趋化性通常被认为依赖于空间感知，只要存在浓度梯度，细胞就会跟随这些梯度。利用微流控方法，我们发现稳定的中间趋化因子(CCL19和CXCL12)梯度不能促进树突状细胞或中性粒细胞的持续定向迁移。相反，需要增加趋化因子浓度，这意味着时间感应机制控制了对这些配体的长期反应。这种行为被发现依赖于G偶联受体激酶介导的受体信号的负调控，并与对终末激动剂化学吸引剂(C5a)的反应形成对比，C5a的稳定梯度导致持续迁移。这些发现确认时间感知是髓系细胞长距离迁移到中间趋化因子的关键要求，并为在复杂的组织环境中控制免疫细胞运动的机制提供了见解。
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments.