A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia-reperfusion injury
A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia-reperfusion injury
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DOI：
10.1038/sj.ki.5002203
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发表时间：
2007-06-01
影响因子：
19.6
通讯作者：
Lien, Y-H H.
中科院分区：
文献类型：
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作者：
Lai, L-W;Yong, K-C;Lien, Y-H H.
T细胞被认为参与肾缺血再灌注损伤（IRI）的发病机制;然而，早期的研究没有发现损伤后肾脏中有显著的T细胞数量。在这项研究中，我们测试的假设，T细胞瞬时浸润肾脏再灌注后，留下T细胞衍生的细胞因子，如干扰素和白细胞介素，从而引发炎症反应。浸润性T细胞的早期上升伴随着循环淋巴细胞和动脉周围淋巴细胞聚集体中的CD 4+细胞的减少。缺血-再灌注（IR）可使多种趋化因子的表达迅速而显著地增加。鞘氨醇-1-磷酸1型受体激动剂已被证明可以保护肾脏免受损伤。在IR之前给予这些激动剂之一显著降低组织学评估的肾损伤、循环淋巴细胞数量和肾T细胞浸润。然而，这种预处理并不影响T细胞趋化因子的增加，但引起肾淋巴系统中CD 4+细胞的增加。我们的结论是，T细胞浸润是IRI后的早期事件，是由几种趋化因子介导的。鞘氨醇-1-磷酸受体激动剂通过抑制肾和肾外淋巴组织的T细胞动员，减少肾损伤和T细胞浸润，尽管产生趋化因子。
T cells are thought to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI); however, earlier studies have not found significant T-cell numbers in the kidney following injury. In this study we test the hypothesis that T cells transiently infiltrate the kidney following reperfusion and leave behind T-cell-derived cytokines such as interferons and interleukins, thus triggering an inflammatory reaction. An early rise of infiltrating T cells was coupled with a decrease in both circulating lymphocytes and CD4+ cells of periarterial lymphocyte aggregates. The renal expression of several chemokines was rapidly and markedly increased by ischemia-reperfusion (IR). Sphingosine-1-phosphate type 1 receptor agonists have been shown to protect kidneys from injury. One of these agonists given before IR significantly reduced histologically assessed renal injury, circulating lymphocyte numbers, and renal T-cell infiltration. This pretreatment did not, however, affect the increase in T-cell chemokines but caused an increase in CD4+ cells in the renal lymphatic system. We conclude that T-cell infiltration is an early event after IRI and is mediated by several chemokines. Sphingosine-1-phosphate receptor agonists reduce renal injury and T-cell infiltration in spite of chemokine generation by inhibiting T-cell mobilization from both renal and extra-renal lymphoid tissue.