Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney.
Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney.
复制标题
DOI：
10.1038/ki.2010.12
复制
发表时间：
2010-05
影响因子：
19.6
通讯作者：
Okusa, Mark D.
中科院分区：
文献类型：
--
作者：
Kinsey, Gilbert R.;Huang, Liping;Vergis, Amy L.;Li, Li;Okusa, Mark D.
缺血-再灌注是急性肾损伤的主要原因，炎症在肾缺血-再灌注损伤（IRI）的发病机制中已被证实是一个有害的过程。肾脏有能力通过一段非致死期的缺血进行预处理，使肾脏不易发生进一步的缺血引起的功能障碍（缺血预处理：IPC）。调节性T （Treg）细胞是抑制免疫反应的淋巴细胞。我们假设IPC是由Treg细胞部分介导的。为了验证这一点，我们在第0天对小鼠进行24分钟的双侧肾脏IRI或假手术，然后在第7天进行28分钟的IRI (IPC = IRI/IRI；非IPC = sham /IRI)，建立了延迟IPC模型。IPC显著抑制中性粒细胞和巨噬细胞的积累、肾小管坏死和IRI引起的肾功能丧失。初始24min IRI导致肾CD4+CD25+FoxP3+和CD4+CD25+IL-10+ Treg细胞在再灌注7天后显著增加。在预处理小鼠中使用Treg细胞消耗抗体（PC61）逆转IPC对肾中性粒细胞积累的影响，并部分抑制IPC的功能和组织学保护作用。在naïve小鼠中，在IR之前过继转移Treg细胞，模拟IPC对肾脏的保护和抗炎作用。这些结果表明，炎症的抑制和肾保护的很大一部分，由延迟IPC传递，是由Treg细胞介导的。
Ischemia-reperfusion is a major cause of acute kidney injury and inflammation has been well-established as a detrimental process in the pathogenesis of kidney ischemia reperfusion injury (IRI). The kidney has the ability to be preconditioned by a non-lethal period of ischemia, rendering the kidney refractory to further ischemia-induced dysfunction (ischemic preconditioning: IPC). Regulatory T (Treg) cells are lymphocytes that suppress immune responses. We hypothesized that IPC is partially mediated by Treg cells. To test this, a model of delayed IPC was used by subjecting mice to 24 min of bilateral renal IRI or sham surgery on day 0, then 28 min IRI on day 7 (IPC = IRI/IRI; non-IPC = Sham/IRI). IPC significantly inhibited the accumulation of neutrophils and macrophages, tubular necrosis and loss of kidney function induced by IRI. The initial 24 min IRI caused a significant increase in kidney CD4+CD25+FoxP3+ and CD4+CD25+IL-10+ Treg cells at 7 days of reperfusion. Use of a Treg cell-depleting antibody (PC61) in preconditioned mice reversed the effect of IPC on kidney neutrophil accumulation and partially inhibited the functional and histological protection of IPC. Adoptive transfer of Treg cells, prior to IR, in naïve mice, mimicked the protective and anti-inflammatory effects of IPC on the kidney. These results demonstrate that suppression of inflammation and a significant fraction of kidney protection, imparted by delayed IPC, is mediated by Treg cells.
登录
查看更多内容
影响因子：
19.6
作者：
Awad, Alaa S.;Rouse, Michael;Huang, Liping;Vergis, Amy L.;Reutershan, Joerg;Cathro, Helen P.;Linden, Joel;Okusa, Mark D.
通讯作者：
Okusa, Mark D.
影响因子：
13.6
作者：
Kielar, ML;John, R;Lu, CY
通讯作者：
Lu, CY
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
13.6
作者：
Ishani, Areef;Xue, Jay L.;Collins, Allan J.
通讯作者：
Collins, Allan J.
DOI：
10.1152/ajprenal.00378.2004
发表时间：
2005-04-01
影响因子：
4.2
作者：
Day, YJ;Huang, L;Okusa, MD
通讯作者：
Okusa, MD