Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.
Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.
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DOI：
10.1084/jem.20121462
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发表时间：
2013-03-11
期刊：
影响因子：
--
通讯作者：
Ludewig B
中科院分区：
文献类型：
--
作者：
Onder L;Danuser R;Scandella E;Firner S;Chai Q;Hehlgans T;Stein JV;Ludewig B
内皮细胞消融淋巴毒素β受体导致周围淋巴结和正常高内皮区发育失败，从而损害淋巴细胞归巢。淋巴结（LNs）的发育和LN间质细胞微环境的形成依赖于淋巴素β受体（LTβR）信号传导。特别是，间充质淋巴组织组织者和造血淋巴组织诱导细胞之间的ltβ r依赖的串扰被认为是这些过程的关键。在这里，我们评估了内皮细胞（EC）限制性LTβR信号是否影响LN的发展和血管LN微环境。通过ec特异性消融小鼠LTβR，我们发现条条性LTβR缺乏的动物不能产生显著比例的外周LNs。然而，残余的LNs显示高内皮小静脉（HEVs）的形成受损。小静脉失去了其立方体形状，片段长度和分支点减少，粘附分子和组成趋化因子表达减少。由于ec -淋巴细胞相互作用的改变，淋巴细胞向外周LNs的归巢明显受损。因此，本研究确定了内皮细胞是一个重要的LTβR依赖的淋巴组织组织者细胞群，并表明持续触发LN内皮细胞上的LTβR对淋巴细胞稳态至关重要。
Endothelial cell ablation of the lymphotoxin-β receptor results in failure to develop peripheral lymph nodes and normal high endothelial venues, which impairs lymphocyte homing. The development of lymph nodes (LNs) and formation of LN stromal cell microenvironments is dependent on lymphotoxin-β receptor (LTβR) signaling. In particular, the LTβR-dependent crosstalk between mesenchymal lymphoid tissue organizer and hematopoietic lymphoid tissue inducer cells has been regarded as critical for these processes. Here, we assessed whether endothelial cell (EC)–restricted LTβR signaling impacts on LN development and the vascular LN microenvironment. Using EC-specific ablation of LTβR in mice, we found that conditionally LTβR-deficient animals failed to develop a significant proportion of their peripheral LNs. However, remnant LNs showed impaired formation of high endothelial venules (HEVs). Venules had lost their cuboidal shape, showed reduced segment length and branching points, and reduced adhesion molecule and constitutive chemokine expression. Due to the altered EC–lymphocyte interaction, homing of lymphocytes to peripheral LNs was significantly impaired. Thus, this study identifies ECs as an important LTβR-dependent lymphoid tissue organizer cell population and indicates that continuous triggering of the LTβR on LN ECs is critical for lymphocyte homeostasis.
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DOI：
10.1084/jem.20021294
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luther SA;Ansel KM;Cyster JG
通讯作者：
Cyster JG
影响因子：
2.5
作者：
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DOI：
10.1073/pnas.1009968107
发表时间：
2010-11-23
影响因子：
11.1
作者：
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通讯作者：
Cyster, Jason G.
DOI：
10.4049/jimmunol.1101724
发表时间：
2011-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
Lu TT
影响因子：
4.4
作者：
Wimmer, Nadin;Huber, Barbara;Hehlgans, Thomas
通讯作者：
Hehlgans, Thomas