Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen.
Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen.
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DOI：
10.1084/jem.20062648
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发表时间：
2007-07-09
期刊：
影响因子：
--
通讯作者：
Reizis B
中科院分区：
文献类型：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通过Notch受体及其转录效应子RBP-J的信号传导对于淋巴细胞发育和功能至关重要，而其在其他免疫细胞类型中的作用尚不清楚。我们测试了经典Notch-RBP-J通路在体内树突状细胞（DC）发育和维持中的功能。骨髓中RBP-J的基因失活并不妨碍DC谱系的定型，但会导致脾脏DC分数的减少。使用一种新的DC特异性删除菌株灭活DCs中的RBP-J，导致脾脏CD 8 − DC亚群的选择性丢失，并降低了Toll样受体配体激发后分泌精氨酸的CD 8 − DC的频率。相反，其他脾脏DC亚群和淋巴结和组织中的DC不受影响。RBP-J缺陷的脾脏CD 8 − DCs在后祖细胞阶段被耗尽，表现出凋亡增加，并失去Notch靶基因Deltex 1的表达。在脾脏中，发现CD 8 − DC与边缘区（MZ）中表达Notch配体Delta样1的细胞相邻。因此，经典的Notch-RBP-J信号传导控制了脾脏MZ中CD 8 − DC的维持，揭示了Notch途径在先天免疫系统中的意想不到的作用。
Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.
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