Regulatory T Cells Promote β-Catenin-Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis
Regulatory T Cells Promote β-Catenin-Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis
复制标题
调节性 T 细胞促进 β-连环蛋白——在辐射诱发的肺纤维化过程中介导的上皮到间质的转变。
DOI：
10.1016/j.ijrobp.2015.05.043
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发表时间：
2015-10-01
影响因子：
7
通讯作者：
Zhu, Maoxiang
中科院分区：
文献类型：
--
作者：
Xiong, Shanshan;Pan, Xiujie;Zhu, Maoxiang
目的：放射性肺纤维化是由胸部放射治疗引起的，严重限制了放射治疗方法。CD 4（+）CD 25（+）FoxP 3（+）调节性T细胞（Treg）以及上皮-间充质转化（EMT）细胞参与多种因素诱导的肺纤维化。然而，TCFs和EMT细胞在放射性肺纤维化中的作用机制尚不清楚。在本研究中，我们调查的影响，THBG对EMT在放射性诱导的肺fibrosis.Methods和材料：小鼠胸部照射（20戈伊），THBG被耗尽的单克隆抗CD 25抗体的腹腔注射后2小时，照射后，每7天，此后。在照射后第3、7和14天以及1、3和6个月处理小鼠。通过流式细胞术测定Treg耗竭的有效性。免疫组化检测肺组织EMT和β-catenin的表达。从小鼠脾脏中分离的TMPs与小鼠肺上皮（MLE）12细胞共同培养，通过流式细胞术和Western blotting检测TMPs对MLE 12细胞EMT和β-catenin的影响。抗-CD 25抗体治疗有效地耗尽了TcB，减弱了辐射诱导的肺纤维化的过程，阻碍了EMT，并减少体内肺上皮细胞中β-连环蛋白的积累。结论：雷公藤多甙能促进放射性肺纤维化的EMT进程。这一过程部分通过β-连环蛋白介导。我们的研究表明，TdR促进EMT的新机制加速了辐射诱导的肺纤维化。(C)由Elsevier Inc.出版。
Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis.Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and beta-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of beta-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and beta-catenin via flow cytometry and Western blotting.Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced beta-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by beta-catenin knockdown in vitro.Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through beta-catenin. Our study suggests anew mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis. (C) 2015 Published by Elsevier Inc.