Selective Impairment of CD4+CD25+Foxp3+Regulatory T cells by paclitaxel is explained by Bcl-2/Bax mediated apoptosis
Selective Impairment of CD4+CD25+Foxp3+Regulatory T cells by paclitaxel is explained by Bcl-2/Bax mediated apoptosis
复制标题
Bcl-2/Bax 介导的细胞凋亡解释了紫杉醇对 CD4 CD25 Foxp3 调节性 T 细胞的选择性损伤
DOI：
10.1016/j.intimp.2010.11.021
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发表时间：
2011-02-01
影响因子：
5.6
通讯作者：
Chu, Yiwei
中科院分区：
文献类型：
--
作者：
Liu, Nan;Zheng, Yijie;Chu, Yiwei
近几十年来，紫杉醇已成为最有效、应用最广泛的化疗药物之一。虽然在我们之前的研究中已经显示出选择性消耗调节性T （Treg）细胞的希望，但其潜在的分子机制仍有待进一步阐明。本研究主要研究紫杉醇对3LL Lewis肿瘤模型中Treg细胞的影响，并探讨其可能参与的分子途径。我们发现紫杉醇显著降低Treg细胞在CD4（+）细胞中的百分比并损害其抑制功能，但效应T （Teff）细胞不受影响。与Teff细胞相比，Treg细胞对紫杉醇介导的体外凋亡表现出较高的敏感性。有趣的是，尽管紫杉醇被认为是一种有丝分裂抑制剂，但微管蛋白并没有参与紫杉醇的选择性功能。暴露于紫杉醇的Treg细胞显示Bcl-2的下调和Bax的上调。阻断Bcl-2通路消除Treg和Teff细胞对紫杉醇反应的差异。这些结果表明，Bcl-2而不是微管蛋白参与了紫杉醇对Treg细胞的独特作用。因此，我们在这里确定了紫杉醇选择性消融Treg细胞的分子途径。(C) 2010 Elsevier B.V.版权所有
Paclitaxel has become one of the most effective and widely used chemotherapeutic agents over the past decades. Although it has shown promise to selectively deplete regulatory T (Treg) cells in our previous study, the underlying molecular mechanism remains to be further elucidated. The present study focused on the effect of paclitaxel on Treg cells in 3LL Lewis tumor model and explored the possible molecular pathways involved in this process. We found that paclitaxel significantly decreased the percentage of Treg cells in CD4(+) cells and impaired their suppressive functions, but effector T (Teff) cells remained unaffected. Compared with Teff cells, Treg cells exhibited a high sensitivity to paclitaxel-mediated apoptosis in vitro. Interestingly, though paclitaxel has been characterized as a mitotic inhibitor, tubulin was not involved in the selective function of paclitaxel. Treg cells exposed to paclitaxel displayed downregulation of Bcl-2 and upregulation of Bax. Blocking the Bcl-2 pathway eliminated the difference between Treg and Teff cells responding to paclitaxel. These results suggest that Bcl-2 rather than tubulin contributes to the distinctive effect of paclitaxel on Treg cells. Therefore, we here identify a molecular pathway through which paclitaxel selectively ablates Treg cells. (C) 2010 Elsevier B.V. All rights reserved.