Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism.
Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism.
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DOI：
10.1038/ki.2015.200
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发表时间：
2015-10
影响因子：
19.6
通讯作者：
Basile DP
中科院分区：
文献类型：
--
作者：
Mehrotra P;Patel JB;Ivancic CM;Collett JA;Basile DP
大鼠从急性肾脏损伤(AKI)恢复后暴露于高盐饮食会加速向慢性肾脏疾病(CKD)的过渡，并依赖于淋巴细胞的活性。在这里，我们测试了高盐饮食是否触发了缺血后肾脏中淋巴细胞的激活，从而加剧了肾脏的炎症和纤维化。雄性SD大鼠喂食0.4%的食盐，造成左侧脑缺血再灌流模型，恢复5周。这导致与假动物相比，CD4+T细胞有轻微的升高。对侧单侧肾切除和高盐饮食(4%)4周可加速慢性肾脏病和间质纤维化。在高盐饮食暴露4周后，肾脏中活化的T细胞比喂盐前的AKI后大鼠增加了3倍。T细胞亚群大部分为IL-17阳性，表明是Th-17细胞。由于血管紧张素II的活性可能影响淋巴细胞的激活，损伤的大鼠在高盐饮食的同时给予AT1R拮抗剂氯沙坦。这显著降低了肾脏Th-17细胞的数量至假手术大鼠的水平，并显著降低了盐诱导的纤维化增加约一半。AKI诱导的CD4+T细胞的体外研究表明，血管紧张素II和细胞外钠增加，而氯沙坦抑制IL-17的表达。因此，饮食盐通过局部RAS的活性调节缺血后恢复肾脏的免疫细胞活性，提示这些细胞参与了AKI后CKD的进展。
Exposure of rats to elevated dietary salt following recovery from acute kidney injury (AKI) accelerates the transition to chronic kidney disease (CKD), and is dependent on lymphocyte activity. Here we tested whether high salt diet triggers lymphocyte activation in post-ischemic kidneys to worsen renal inflammation and fibrosis. Male Sprague- Dawley rats on a 0.4% salt diet were subjected to left unilateral ischemia-reperfusion and allowed to recover for 5 weeks. This resulted in a mild elevation of CD4+ T-cells relative to sham animals. Contralateral unilateral nephrectomy and elevated dietary salt (4%) for 4 extra weeks hastened CKD and interstitial fibrosis. Activated T cells were increased in the kidney 3-fold after 4 weeks of elevated dietary salt exposure relative to post AKI rats prior to salt feeding. The T-cell subset was largely positive for IL-17, indicative of Th-17 cells. Because angiotensin II activity may influence lymphocyte activation, injured rats were given the AT1R antagonist, Losartan, along with high salt diet. This significantly reduced the number of renal Th-17 cells to levels of sham rats, and significantly reduced the salt-induced increase in fibrosis about half. In vitro studies in AKI-primed CD4+ T cells indicated angiotensin II and extracellular sodium enhanced, and Losartan inhibited IL-17 expression. Thus, dietary salt modulates immune cell activity in post ischemic recovering kidneys due to the activity of local RAS suggesting participation of these cells in CKD progression post AKI.