Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing
Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing
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DOI：
10.1172/jci.insight.120546
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发表时间：
2018-07-12
期刊：
影响因子：
8
通讯作者：
Abdi, Reza
中科院分区：
文献类型：
--
作者：
Maarouf, Omar H.;Uehara, Mayuko;Abdi, Reza
肾引流淋巴结(KLN)在肾脏缺血再灌注损伤(IRI)的发病机制及随后的恢复中的作用尚未深入探讨。此外，重复性IRI促进肾纤维化的机制仍知之甚少。在此，我们发现肾脏的IRI与KLN中高内皮微静脉(HEV)的扩张和成纤维细胞网状细胞(FRC)的激活有关，这表现为细胞外基质的显著扩张。淋巴毒素a信号通路介导FRCs的激活，淋巴毒素β受体-免疫球蛋白融合蛋白(LTβr-Ig)慢性治疗可导致KLN的显著改变和肾脏纤维化的加重。去除FRCs减少了KLN中T细胞的激活，改善了急性IRI的肾脏损伤。反复肾IRI与FRC衰老、KLN纤维化和肾脏瘢痕形成相关，这些都可以通过FRC治疗得到改善。因此，我们的研究强调了FRCs在肾脏IRI后损伤的起始和修复阶段的关键作用。
The contribution of the kidney-draining lymph node (KLN) to the pathogenesis of ischemia-reperfusion injury (IRI) of the kidney and its subsequent recovery has not been explored in depth. In addition, the mechanism by which repetitive IRI contributes to renal fibrosis remains poorly understood. Herein, we have found that IRI of the kidney is associated with expansion of high endothelial venules (HEVs) and activation of fibroblastic reticular cells (FRCs) in the KLN, as demonstrated by significant expansion in the extracellular matrix. The lymphotoxin a signaling pathway mediates activation of FRCs, and chronic treatment with lymphotoxin beta receptor-immunoglobulin fusion protein (LT beta r-Ig) resulted in marked alteration of the KLN as well as augmentation of renal fibrosis. Depletion of FRCs reduced T cell activation in the KLN and ameliorated renal injury in acute IRI. Repetitive renal IRI was associated with senescence of FRCs, fibrosis of the KLN, and renal scarring, which were ameliorated by FRC administration. Therefore, our study emphasizes the critical role of FRCs in both the initiation and repair phases of injury following IRI of the kidney.