Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis
Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis
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DOI：
10.1016/j.immuni.2017.05.008
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发表时间：
2017-07-18
期刊：
影响因子：
32.4
通讯作者：
Ludewig, Burkhard
中科院分区：
文献类型：
--
作者：
Onder, Lucas;Moerbe, Urs;Ludewig, Burkhard
淋巴结（Lymph nodes，LN）战略性地位于全身血管和淋巴系统的接合处，以引导针对从外周组织引流的抗原的免疫应答。目前的范式将LN的发展描述为一个程序化的过程，该过程通过间充质淋巴组织组织形成细胞（LTo）和造血淋巴组织诱导细胞（LTi）之间的相互作用来控制。使用细胞类型特异性消融参与淋巴器官发生的关键分子，我们发现LN发展的启动依赖于LTi细胞介导的淋巴内皮细胞（LECs）的激活，并且间充质基质细胞的参与是一个后续事件。LEC激活主要通过NF-κ B受体激活剂（RANK）和非经典NF-κ B途径的信号传导介导，并由LN原基中LTi细胞的1-磷酸鞘氨醇受体依赖性保留控制。最后，发现LTi细胞和LEC之间的非强制性相互作用促进异位LN形成强调了LEC的中心LTo功能。
Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-kappa B (RANK) and the non-canonical NF-kappa B pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs.