The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.
The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.
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DOI：
10.1038/ki.2011.458
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发表时间：
2012-05
影响因子：
19.6
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中科院分区：
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肾移植相关的缺血/再灌注损伤会导致严重的急性损伤，影响移植肾的早期功能和远期疗效。为了确定肾树突状细胞在早期先天缺血/再灌注损伤和随后的适应性免疫反应的发展中是否起作用，我们研究了肾缺血/再灌注损伤早期和晚期移植肾和宿主浸润性树突状细胞的行为和功能。野生型转GFP转基因大鼠肾移植分别在冷藏和非冷藏条件下进行。冷藏移植肾缺血/再灌注损伤10周后可出现间质纤维化和肾小管萎缩的组织病理学改变，并伴有间质纤维化和炎症介质的mRNAs表达上调。在正常大鼠肾脏中，我们发现了两类树突状细胞，主要是CD103+−CD11b/c+细胞和少量CD103+CD11b/c+细胞。未经冷藏的肾移植后，移植物维持CD103GFP，但不保持−阴性的肾树突状细胞达10周。相反，这两个细胞亚群从冷藏移植物中消失，这与显著的绿色荧光蛋白表达宿主CD11b/c+细胞的渗透有关，其中包括产生肿瘤坏死因子-α表型的CD103+树突状细胞。移植物/宿主树突状细胞群的这些变化与宿主具有效应/效应记忆表型的CD_4+T细胞的逐渐渗透和干扰素-γ的分泌有关。因此，移植肾缺血/再灌注损伤导致移植物树突状细胞丢失，并与宿主树突状细胞和T细胞募集有关。肾内树突状细胞可能作为保护性调节网络发挥作用。
Ischemia/reperfusion injury associated with kidney transplantation induces profound acute injury, influences early graft function and affects long-term graft outcomes. To determine whether renal dendritic cells play any role during initial innate ischemia/reperfusion injury and the subsequent development of adaptive immune responses, we studied the behavior and function of renal graft and host infiltrating dendritic cells during early and late phases of renal ischemia/reperfusion injury. Wild type to GFP-transgenic rat kidney transplantation was performed with and without 24 hours cold storage. Ischemia/reperfusion injury in cold stored grafts resulted in histopathological changes of interstitial fibrosis and tubular atrophy by 10 weeks accompanied by upregulation of mRNAs of mediators of interstitial fibrosis and inflammation. In normal rat kidneys we identified two populations of renal dendritic cells, predominant CD103−CD11b/c+ and minor CD103+CD11b/c+ cells. After transplantation without cold storage, grafts maintained CD103− but not CD103+ GFP-negative renal dendritic cells for 10 weeks. In contrast, both cell subsets disappeared from cold stored grafts, which associated with a significant GFP-expressing host CD11b/c+ cell infiltration that included CD103+ dendritic cells with a TNF-α producing phenotype. These changes in graft/host dendritic cell populations were associated with progressive infiltration of host CD4+ T cells with effector/effector-memory phenotypes and IFN-γ secretion. Thus, renal graft ischemia/reperfusion injury causes graft dendritic cell loss and was associated with progressive host dendritic cell and T cell recruitment. Renal resident dendritic cells might function as a protective regulatory network.