Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis.

Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis.
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成纤维细胞网状细胞和B细胞之间的相互作用促进肠系膜淋巴结淋巴管生成。

DOI:
10.1038/s41467-017-00504-9
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发表时间:
2017-08-28
影响因子:
16.6
通讯作者:
Harris NL
Harris NL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dubey LK;Karempudi P;Luther SA;Ludewig B;Harris NL

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淋巴生长(淋巴管生成)在淋巴结内的功能促进树突状细胞进入和效应淋巴细胞的出口,以应对感染或炎症。在这里,我们证明了淋巴毒素β受体(LTβR)信号通过表达淋巴毒素的B细胞传递给成纤维网状细胞(FRCs)在蠕虫感染后驱动肠系膜淋巴结淋巴管生成中的关键作用。在成纤维网状细胞上结扎LTβR导致B细胞活化因子(BAFF)的产生,该因子与白细胞介素-4 (IL-4)协同促进B细胞产生淋巴管生成因子、血管内皮生长因子(VEGF)-A和VEGF- c。此外,BAFF-IL-4协同作用增强抗原活化B细胞淋巴蛋白的表达,进一步促进B细胞与成纤维网状细胞的相互作用。这些结果表明淋巴毒素依赖的B细胞- frc串扰在促进和维持免疫反应的淋巴网络扩张中的重要性。淋巴结的生长是对感染的反应,需要淋巴管生成。Dubey等研究表明,寄生虫感染后肠系膜淋巴结的淋巴管生成依赖于B和纤维母细胞网状细胞(FRCs)之间的信号通路,FRCs通过释放B细胞激活因子对B细胞分泌的淋巴素作出反应。
Lymphatic growth (lymphangiogenesis) within lymph nodes functions to promote dendritic cell entry and effector lymphocyte egress in response to infection or inflammation. Here we demonstrate a crucial role for lymphotoxin-beta receptor (LTβR) signaling to fibroblastic reticular cells (FRCs) by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. LTβR ligation on fibroblastic reticular cells leads to the production of B-cell-activating factor (BAFF), which synergized with interleukin-4 (IL-4) to promote the production of the lymphangiogenic factors, vascular endothelial growth factors (VEGF)-A and VEGF-C, by B cells. In addition, the BAFF-IL-4 synergy augments expression of lymphotoxin by antigen-activated B cells, promoting further B cell–fibroblastic reticular cell interactions. These results underlie the importance of lymphotoxin-dependent B cell–FRC cross talk in driving the expansion of lymphatic networks that function to promote and maintain immune responsiveness. The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor.
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