Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche
Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche
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DOI：
10.1016/j.immuni.2019.05.008
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发表时间：
2019-06-18
期刊：
影响因子：
32.4
通讯作者：
Mueller, Christopher G.
中科院分区：
文献类型：
--
作者：
Camara, Abdouramane;Cordeiro, Olga G.;Mueller, Christopher G.
组织驻留巨噬细胞接受集中在细胞龛中的特定信号，这些信号指导它们的细胞分化和维持遗传程序。在此，我们发现淋巴结的淋巴组织者和边缘网状基质细胞中细胞因子RANKL的缺乏导致CD169（+）窦状隙巨噬细胞（SM）（包括被膜下和髓质亚型）的丢失。在SM中具有靶向RANK缺陷的小鼠中，被膜下SM分化受损。淋巴管内皮细胞（LEC）中时间控制的RANK清除显示，两种SM亚型的分化需要胚胎发生期间和出生后不久的淋巴RANK激活。此外，RANK表达LEC是必要的SM恢复后炎症诱导的细胞损失。因此，间充质细胞和LEC之间的合作形成了支持SM分化和炎症后重建的生态位环境。
Tissue-resident macrophages are receptive to specific signals concentrated in cellular niches that direct their cell differentiation and maintenance genetic programs. Here, we found that deficiency of the cytokine RANKL in lymphoid tissue organizers and marginal reticular stromal cells of lymph nodes resulted in the loss of the CD169(+) sinusoidal macrophages (SMs) comprising the subcapsular and the medullary subtypes. Subcapsular SM differentiation was impaired in mice with targeted RANK deficiency in SMs. Temporally controlled RANK removal in lymphatic endothelial cells (LECs) revealed that lymphatic RANK activation during embryogenesis and shortly after birth was required for the differentiation of both SM subtypes. Moreover, RANK expression by LECs was necessary for SM restoration after inflammation-induced cell loss. Thus, cooperation between mesenchymal cells and LECs shapes a niche environment that supports SM differentiation and reconstitution after inflammation.