The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment.
The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment.
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DOI：
10.1084/jem.193.9.1105
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发表时间：
2001-05-07
期刊：
影响因子：
--
通讯作者：
Haraldsen G
中科院分区：
文献类型：
--
作者：
Baekkevold ES;Yamanaka T;Palframan RT;Carlsen HS;Reinholt FP;von Andrian UH;Brandtzaeg P;Haraldsen G
淋巴细胞归巢到次级淋巴组织是由高内皮微静脉（HEV）中淋巴细胞和内皮细胞之间的多步骤相互作用定义的。在最初的选择素介导的束缚和滚动后，淋巴细胞的牢固粘附需要淋巴细胞整合素β的快速上调。该步骤部分由HEV衍生的趋化因子SLC（次级淋巴组织趋化因子，或CCL 21）介导，其结合淋巴细胞上的CC趋化因子受体（CCR）7。然而，CC趋化因子ELC（Epstein-Barr病毒诱导的分子1配体趋化因子，或CCL 19）共享相同的受体，并且在淋巴器官的T细胞区域中已经观察到ELC转录物。在这里，我们表明，血管周围的ELC是transcytosed到腔表面的HEV，使有效的T细胞归巢淋巴结。人扁桃体组织切片原位杂交显示HEV中无ELC mRNA表达，但免疫组化显示HEV细胞胞浆囊泡中有ELC蛋白。此外，注射到小鼠足垫中的ELC进入引流淋巴结并由HEV呈递。最后，在缺乏功能相关的ELC和SLC的小鼠（plt/plt小鼠）中皮内注射ELC恢复了T细胞向引流淋巴结的运输，与SLC一样有效。我们的结论是，血管周围ELC是transcytosed到腔表面的HEV和参与CCR 7介导的触发淋巴细胞阻滞。
Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus–induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.
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影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
Picker, LJ
DOI：
10.1084/jem.192.10.1425
发表时间：
2000-11-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gretz JE;Norbury CC;Anderson AO;Proudfoot AE;Shaw S
通讯作者：
Shaw S
DOI：
10.1073/pnas.97.23.12694
发表时间：
2000-11-07
影响因子：
11.1
作者：
Luther, SA;Tang, HL;Cyster, JG
通讯作者：
Cyster, JG
影响因子：
6
作者：
Girard, JP;Baekkevold, ES;Amalric, F
通讯作者：
Amalric, F