Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs.

Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs.
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CXCR5和CCR7的合作机制在继发性淋巴机构的开发和组织中。

DOI:
10.1084/jem.20030169
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发表时间:
2003-05-05
影响因子:
15.3
通讯作者:
Förster, R
Förster, R
中科院分区:
医学1区
文献类型:
--
作者:
Ohl, L;Henning, G;Krautwald, S;Lipp, M;Hardtke, S;Bernhardt, G;Pabst, O;Förster, R

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稳态趋化因子参与次级淋巴器官的发育,然后参与这些组织的功能组织。淋巴结(LN)和派尔集合淋巴结(Peyer's patch)的发育取决于CD 3 − CD 4+白细胞介素(IL)-7 R细胞在未来器官发育部位的募集。CD 3-CD 4 + IL-7 R αhi细胞表达趋化因子受体CXCR 5,并可能被间充质细胞分泌的配体CXCL 13所吸引。间充质细胞也分泌CCL 19,CCR 7的配体,但目前尚不清楚CCR 7和CCL 19是否对次级淋巴器官发育很重要。分析CXCR 5 −/− CCR 7 −/−双缺陷小鼠,我们现在发现这些小鼠缺乏所有检查的外周淋巴结,这表明两种受体在次级淋巴器官发育中的重要作用。我们证明,CD 3 − CD 4 + IL-7 R αhi细胞表达CXCR 5和CCR 7,表明两种受体在次级淋巴器官发育的早期阶段相互作用。此外,CXCR 5 −/− CCR 7 −/−小鼠显示肠系膜LN和脾脏的结构严重紊乱。由于B细胞向白色髓中的迁移受损,CXCR 5 −/− CCR 7 −/−小鼠不能发育B细胞滤泡,但在脾脏中显示出小簇无组织的淋巴细胞。这些数据证明了CXCR 5和CCR 7在淋巴器官器官发生和组织中的协同功能。
Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3− CD4+ interleukin (IL)-7Rαhi cells to sites of future organ development. CD3− CD4+ IL-7Rαhi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5−/− CCR7−/− double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3− CD4+ IL-7Rαhi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5−/− CCR7−/− mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5−/− CCR7−/− mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization.
DOI: 10.1084/jem.194.11.1649
发表时间: 2001-12-03
影响因子: 15.3
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