The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues.
The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissues.
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DOI：
10.1084/jem.190.5.629
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发表时间：
1999-09-06
期刊：
影响因子：
--
通讯作者：
Fu YX
中科院分区：
文献类型：
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作者：
Wu Q;Wang Y;Wang J;Hedgeman EO;Browning JL;Fu YX
虽然包括肿瘤坏死因子（TNF）在内的几种细胞因子可以促进体外树突状细胞（DC）的生长，但体内天然调节DC发育和功能的细胞因子尚未得到很好的定义。在这里，我们报告，膜光敏素（LT），而不是TNF，调节脾脏中的DC的迁移。缺乏膜LTα/β和LTα3的LTα−/−小鼠显示脾脏中DC数量显著减少。与野生型小鼠和TNF-/-小鼠在T细胞区和边缘区周围密集聚集的DC不同，LTα-/-小鼠的脾脏DC是随机分布的。LTα−/−小鼠淋巴组织中DC数量的减少与非淋巴组织中DC数量的增加相关。当提供额外的LT表达细胞时，LTα−/−小鼠中脾脏DC的数量恢复。在野生型小鼠中阻断膜LTα/β可显著减少DC在淋巴组织中的积聚。这些数据表明，膜LT是脾脏中DC存在的必需配体。TNF受体是可溶性LTα3和TNF-α3三聚体的受体，TNF受体缺陷的小鼠具有正常数量的DC。然而，LTβR−/−小鼠显示DC数量减少，与缺乏膜LT α/β的小鼠相似。综上所述，这些结果支持了这样的观点，即淋巴组织中DC的存在需要通过膜LTα/β的LTβR信号传导。
Although several cytokines, including tumor necrosis factor (TNF), can promote the growth of dendritic cells (DCs) in vitro, the cytokines that naturally regulate DC development and function in vivo have not been well defined. Here, we report that membrane lymphotoxin (LT), instead of TNF, regulates the migration of DCs in the spleen. LTα−/− mice, lacking membrane LTα/β and LTα3, show markedly reduced numbers of DCs in the spleen. Unlike wild-type mice and TNF−/− mice that have densely clustered DCs in the T cell zone and around the marginal zone, splenic DCs in LTα−/− mice are randomly distributed. The reduced number of DCs in lymphoid tissues of LTα−/− mice is associated with an increased number of DCs in nonlymphoid tissues. The number of splenic DCs in LTα−/− mice is restored when additional LT-expressing cells are provided. Blocking membrane LTα/β in wild-type mice markedly diminishes the accumulation of DCs in lymphoid tissues. These data suggest that membrane LT is an essential ligand for the presence of DCs in the spleen. Mice deficient in TNF receptor, which is the receptor for both soluble LTα3 and TNF-α3 trimers, have normal numbers of DCs. However, LTβR−/− mice show reduced numbers of DCs, similar to the mice lacking membrane LT α/β. Taken together, these results support the notion that the signaling via LTβR by membrane LTα/β is required for the presence of DCs in lymphoid tissues.