Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells.
Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells.
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DOI：
10.4049/jimmunol.1101724
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Lu TT
中科院分区：
文献类型：
--
作者：
Chyou S;Benahmed F;Chen J;Kumar V;Tian S;Lipp M;Lu TT
淋巴结血管在免疫细胞的支持和运输中起重要作用。血管系统是血管-基质区室的组成部分，还包括淋巴管系统和成纤维网状细胞（FRC）。在免疫应答期间，随着淋巴结肿胀，血管系统经历快速增殖性生长，其最初依赖于CD 11 c+细胞和VEGF，但不依赖于淋巴细胞。淋巴管系统以相似的动力学和VEGF依赖性生长，表明血液和淋巴管生长的共同调节，但淋巴管生长已被证明是B细胞依赖性的。在这里，我们表明，血管，淋巴管和FRC的生长协调调节，并确定两个不同的阶段的血管基质生长的起始阶段，其特征在于上调血管基质增殖，和随后的扩张阶段。起始阶段是CD 11 c+细胞依赖性和T/B细胞非依赖性的，而扩增阶段是依赖于B和T细胞一起的。使用CCR 7 −/−小鼠和选择性去除迁移性皮肤树突状细胞，我们表明内源性皮肤来源的树突状细胞在起始阶段并不重要，并揭示了CCR 7的适度调节作用。最后，我们发现FRC VEGF表达在启动过程中上调，树突状细胞可以刺激成纤维细胞VEGF的增加，这表明淋巴结驻留的CD 11 c+细胞部分通过刺激FRC上调VEGF来协调血液和淋巴管血管生长的启动。这些结果说明了淋巴结微环境是如何由它所支持的细胞塑造的。
Lymph node blood vessels play important roles in the support and trafficking of immune cells. The blood vasculature is a component of the vascular-stromal compartment that also includes the lymphatic vasculature and fibroblastic reticular cells (FRCs). During immune responses, as lymph nodes swell, the blood vasculature undergoes a rapid proliferative growth that is initially dependent on CD11c+ cells and VEGF but is independent of lymphocytes. The lymphatic vasculature grows with similar kinetics and VEGF dependence, suggesting co-regulation of blood and lymphatic vascular growth, but lymphatic growth has been shown to be B cell-dependent. Here we show that blood vascular, lymphatic, and FRC growth are coordinately regulated and identify two distinct phases of vascular-stromal growth—an initiation phase, characterized by upregulated vascular-stromal proliferation, and a subsequent expansion phase. The initiation phase is CD11c+ cell-dependent and T/B cell-independent while the expansion phase is dependent on B and T cells together. Using CCR7−/− mice and selective depletion of migratory skin dendritic cells, we show that endogenous skin-derived dendritic cells are not important during the initiation phase and uncover a modest regulatory role for CCR7. Finally, we show that FRC VEGF expression is upregulated during initiation and that dendritic cells can stimulate increased fibroblastic VEGF, suggesting the scenario that lymph node-resident CD11c+ cells orchestrate the initiation of blood and lymphatic vascular growth in part by stimulating FRCs to upregulate VEGF. These results illustrate how the lymph node microenvironment is shaped by the cells it supports.
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DOI：
10.1084/jem.20071966
发表时间：
2007-12-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bursch LS;Wang L;Igyarto B;Kissenpfennig A;Malissen B;Kaplan DH;Hogquist KA
通讯作者：
Hogquist KA
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
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
影响因子：
20.3
作者：
Halin, Cornelia;Tobler, Nadja E.;Detmar, Michael
通讯作者：
Detmar, Michael
影响因子：
32.4
作者：
Kataru, Raghu P.;Kim, Honsoul;Koh, Gou Young
通讯作者：
Koh, Gou Young