Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis
Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis
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肾脏和淋巴结中的淋巴管生成介导肾脏炎症和纤维化
DOI：
10.1126/sciadv.aaw5075
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发表时间：
2019-06-01
期刊：
影响因子：
13.6
通讯作者：
Xu, Gang
中科院分区：
文献类型：
--
作者：
Pei, Guangchang;Yao, Ying;Xu, Gang
肾脏和肾脏引流淋巴结（RDLN）中扩张的淋巴管（LV）促进肾内炎症和纤维化。淋巴管生成与慢性肾病（CKD）相关，并发生在肾移植后。在这里，我们证明，扩大淋巴管（LV）在肾脏和相应的肾引流淋巴结（RDLN）在促进肾内炎症和纤维化肾损伤后发挥关键作用。我们的研究表明，肾脏和RDLN中的淋巴管生成是由表达必需C-C趋化因子配体21（CCL 21）的预先存在的淋巴管内皮细胞增殖驱动的。新的损伤诱导的LV也表达CCL 21，刺激更多的CCR 7+树突状细胞（DC）和淋巴细胞募集到RDLN和脾脏中，导致全身淋巴细胞扩增。损伤诱导的肾内炎症和纤维化可以通过阻断CCR 7+细胞向RDLN和脾脏的募集或抑制淋巴管生成来减轻。阐明淋巴管生成在促进肾内炎症和纤维化中的作用提供了一个关键的见解，可以促进新的治疗策略的开发，以防止CKD相关纤维化的进展。
Expanded lymphatic vessels (LVs) in kidneys and renal draining lymph nodes (RDLNs) promote intrarenal inflammation and fibrosis. Lymphangiogenesis is associated with chronic kidney disease (CKD) and occurs following kidney transplant. Here, we demonstrate that expanding lymphatic vessels (LVs) in kidneys and corresponding renal draining lymph nodes (RDLNs) play critical roles in promoting intrarenal inflammation and fibrosis following renal injury. Our studies show that lymphangiogenesis in the kidney and RDLN is driven by proliferation of preexisting lymphatic endothelium expressing the essential C-C chemokine ligand 21 (CCL21). New injury-induced LVs also express CCL21, stimulating recruitment of more CCR7+ dendritic cells (DCs) and lymphocytes into both RDLNs and spleen, resulting in a systemic lymphocyte expansion. Injury-induced intrarenal inflammation and fibrosis could be attenuated by blocking the recruitment of CCR7+ cells into RDLN and spleen or inhibiting lymphangiogenesis. Elucidating the role of lymphangiogenesis in promoting intrarenal inflammation and fibrosis provides a key insight that can facilitate the development of novel therapeutic strategies to prevent progression of CKD-associated fibrosis.