Up-regulation of Th17 cells may underlie inhibition of Treg development caused by immunization with activated syngeneic T cells.
Up-regulation of Th17 cells may underlie inhibition of Treg development caused by immunization with activated syngeneic T cells.
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DOI：
10.1371/journal.pone.0027289
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Wang L;Lin J;Zhou Z;Huo R;Shen B;Sun Y;Li N
我们以前的工作表明，用减毒活化的同基因T细胞（aTCV）免疫的小鼠导致Treg功能减弱，这导致抗肿瘤免疫增强。众所周知，DC在控制Th细胞分化中起着非常重要的作用，但DC是否参与免疫小鼠中Treg的减毒尚不清楚。在这项研究中，我们提供了证据表明，aTCV免疫后增加的成熟DC（mDC）使Th 17分化偏斜，这导致通过IL-6信号通路抑制Treg分化。在本研究中，我们发现与对照组相比，免疫小鼠中mDC的频率显著增加，伴有较低的Treg细胞。此外，DC和来自免疫小鼠的血清在体外分别抑制Treg分化。从骨髓前体细胞在体外产生的mDC强烈抑制Treg发育，同时驱动Th 17分化和升高的IL-6产生。然而，PD-L1，一种有效的Treg诱导剂，对Treg下调没有显示作用。用transwell系统进行的测定显示，细胞-细胞接触对于IL-6产生至阈值以激活Th 17转录因子RORγt和抑制Treg对应物Foxp 3是必需的。我们的研究结果提示上调Th 17的发育可能是aTCV免疫诱导的抗肿瘤免疫增强机制之一，为抗肿瘤免疫的众多机制提供了新的见解。
Our previous work showed that mice immunized with attenuated activated syngeneic T cells (aTCV) led to damping Treg function which resulted in enhancing anti-tumor immunity. It is well known that DC plays a very important role in controlling Th cell differentiation; whether DC involves Treg attenuation in immunized mice remained unknown. In this study, we provided evidence that increased mature DC (mDC) after immunization with aTCV skewed Th17 differentiation, which resulted in inhibition of Treg differentiation through IL-6 signaling pathway. In the present study, we found that the frequency of mDCs increased dramatically in the immunized mice accompanied by lower Treg cells compared to the controls. Moreover, both DCs and serum derived from the immunized mice suppressed Treg differentiation in vitro, respectively. mDCs generated from bone marrow precursor cells in vitro strongly inhibited Treg development and simultaneously drove Th17 differentiation with elevated IL-6 production. However, PD-L1, a potent Treg inducer did not show effect on Treg down-regulation. Assay with transwell systems showed that cell-cell contact was necessary for IL-6 production to a threshold to activate Th17 transcriptional factor RORγt and to inhibit Treg counterpart Foxp3. Our results implicate up-regulated Th17 development might be one of mechanisms of enhancing anti-tumor immunity induced by immunization with aTCV, which provide a novel insight in numerous mechanisms responsible for anti-tumor immunity.
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影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
募集高危险性CD8（+）T细胞的潜在池募集到抗肿瘤免疫反应中。
DOI：
10.1084/jem.20042167
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ercolini AM;Ladle BH;Manning EA;Pfannenstiel LW;Armstrong TD;Machiels JP;Bieler JG;Emens LA;Reilly RT;Jaffee EM
通讯作者：
Jaffee EM
影响因子：
2.8
作者：
Canderan, Glenda;Dellabona, Paolo
通讯作者：
Dellabona, Paolo
影响因子：
5.6
作者：
Langroudi, Ladan;Hassan, Zuhir Muhammad;Noori, Shokoofe
通讯作者：
Noori, Shokoofe