CD4+Foxp3+ Regulatory T‐cell Impairment by Paclitaxel is Independent of Toll‐like Receptor 4
CD4+Foxp3+ Regulatory T‐cell Impairment by Paclitaxel is Independent of Toll‐like Receptor 4
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DOI：
10.1111/j.1365-3083.2011.02514.x
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发表时间：
2011-04
影响因子：
3.7
通讯作者：
Ying Zhu;Nan Liu;Shudao Xiong;Yijie Zheng;Yiwei Chu
中科院分区：
文献类型：
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作者：
Ying Zhu;Nan Liu;Shudao Xiong;Yijie Zheng;Yiwei Chu
紫杉醇（PTX）是目前临床上应用最广泛的抗肿瘤化疗药物之一。其对免疫系统的影响已成为近年来研究的热点。在这里，我们证明了PTX不仅在体外和体内降低了CD 4 + Foxp 3+调节性T（Treg）细胞的百分比，而且还损害了Treg细胞的细胞活力和细胞因子产生，而不是CD 4 + Foxp 3 −效应T（Teff）细胞。由于已报道PTX模拟LPS的活性以触发巨噬细胞中的Toll样受体4（TLR 4）信号传导途径，因此我们研究了TLR 4在PTX作用中的可能作用。然而，尽管Treg细胞上的TLR 4表达高于Teff细胞上的TLR 4表达，但在PTX处理后，Treg和Teff细胞中的表达水平保持不变。Treg和Teff细胞的表面分子和活化标志物也没有改变。进一步的研究表明，PTX对TLR 4信号转导缺陷的TLR 4 −/−小鼠的作用与C57 BL/6小鼠在体内和体外的作用相似。这些数据表明PTX对Treg细胞的选择性损伤不依赖于TLR 4。
Paclitaxel (PTX) is one of the most widely used clinical antitumour drugs in chemotherapy nowadays. Its effect on immune system has become a hot spot of research in recent years. Here, we demonstrated that PTX not only decreased the percentage of CD4+Foxp3+ regulatory T (Treg) cells both in vitro and in vivo but also impaired cell viability and cytokine production of Treg cells rather than CD4+Foxp3− effector T (Teff) cells. As PTX has been reported to mimic the activity of LPS to trigger the toll‐like receptor 4 (TLR4) signalling pathway in macrophages, we investigated the possible role of TLR4 in the effect of PTX. However, although TLR4 expression on Treg cells was higher than that on Teff cells, the expression level remained unaltered in both Treg and Teff cells after PTX treatment. Surface molecules and activation markers in Treg and Teff cells did not change, either. Further study showed that the effect of PTX on TLR4−/− mice deficient in TLR4 signalling was similar to that on C57BL/6 mice both in vivo and in vitro. These data indicate that the selective impairment of Treg cells by PTX is independent of TLR4.