Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury.
Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury.
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DOI：
10.1038/ki.2011.412
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发表时间：
2012-05
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
调节性T细胞（Regulatory T cells，Tcells）是外周免疫耐受系统的重要组成部分，已成为治疗炎症过程的免疫调节剂。然而，这种治疗选择受到分离和扩增所需TdR引起的问题的阻碍。在这里，我们使用了一种替代方法，用药理学试剂刺激TGFAP，以达到免疫抑制作用。在双侧肾缺血/再灌注损伤的早期阶段，发现用天然存在的鞘氨醇N，N-二甲基鞘氨醇（DMS）预处理小鼠可增加组织浸润性T效应物（Teff，CD 4 + Foxp 3 −）和Teff（CD 4 + Foxp 3+）。DMS本身对肾功能或组织病理学没有影响，但在非缺血肾（假手术）中快速和短暂地增加Teff和Teff，并增加趋化因子CXCL 9、CCL 5和CXCL 10的表达。这种肾保护作用被Treg抑制剂、抗CTLA-4或抗CD 25单克隆抗体的给药所消除，这表明TcR在DMS诱导的肾保护中起关键作用。因此，通过DMS将TdR募集到肾脏，改善急性肾损伤，并提供控制炎症性疾病的新方法。
Regulatory T cells (Tregs) are key components of the peripheral tolerance system and have become an immunotherapeutic agent for treating inflammatory processes. This therapeutic option, however, is hampered by problems arising from isolating and expanding desirable Tregs. Here we used an alternative approach with a pharmacologic agent to stimulate Tregs to achieve immunosuppressive effects. Pretreatment of mice with the naturally occurring sphingosine N, N-dimethylsphingosine (DMS) was found to increases both tissue infiltrating T effectors (Teff, CD4+Foxp3−) and Tregs (CD4+Foxp3+), in the early phase of bilateral renal ischemia/reperfusion injury. DMS itself had no effects on renal function or histopathology, but rapidly and transiently increased both Teff and Tregs and increased the expression of chemokines CXCL9, CCL5, and CXCL10 in non-ischemic kidneys (sham operation). This renoprotection was abolished by administration of the Treg suppressing agents, anti-CTLA-4 or anti-CD25 monoclonal antibodies, suggesting that Tregs play a key role in DMS-induced renoprotection. Thus, Tregs recruited to the kidney by DMS, ameliorate acute kidney injury and provide a new approach to control inflammatory diseases.
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影响因子：
19.6
作者：
Lai, L-W;Yong, K-C;Lien, Y-H H.
通讯作者：
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影响因子：
19.6
作者：
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通讯作者：
Zuk, A
DOI：
10.1152/ajprenal.00290.2007
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
19.6
作者：
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通讯作者：
Okusa, Mark D.