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Title: Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

Abstract

Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} 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 β-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 β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-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 β-catenin accumulation in lung epithelial cellsmore » 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 β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.« less

Authors:
; ; ;  [1];  [2]; ; ; ; ; ;  [1];  [1]
  1. Beijing Institute of Radiation Medicine, Beijing (China)
  2. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States)
Publication Date:
OSTI Identifier:
22458791
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 93; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTIBODIES; CHEST; EPITHELIUM; FIBROSIS; INTRAPERITONEAL INJECTION; IRRADIATION; LUNGS; MICE; RADIOTHERAPY; RNA; SPLEEN

Citation Formats

Xiong, Shanshan, Pan, Xiujie, Xu, Long, Yang, Zhihua, Guo, Renfeng, Gu, Yongqing, Li, Ruoxi, Wang, Qianjun, Xiao, Fengjun, Du, Li, Zhou, Pingkun, and Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2015.05.043.
Xiong, Shanshan, Pan, Xiujie, Xu, Long, Yang, Zhihua, Guo, Renfeng, Gu, Yongqing, Li, Ruoxi, Wang, Qianjun, Xiao, Fengjun, Du, Li, Zhou, Pingkun, & Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis. United States. doi:10.1016/J.IJROBP.2015.05.043.
Xiong, Shanshan, Pan, Xiujie, Xu, Long, Yang, Zhihua, Guo, Renfeng, Gu, Yongqing, Li, Ruoxi, Wang, Qianjun, Xiao, Fengjun, Du, Li, Zhou, Pingkun, and Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn. Thu . "Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis". United States. doi:10.1016/J.IJROBP.2015.05.043.
@article{osti_22458791,
title = {Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis},
author = {Xiong, Shanshan and Pan, Xiujie and Xu, Long and Yang, Zhihua and Guo, Renfeng and Gu, Yongqing and Li, Ruoxi and Wang, Qianjun and Xiao, Fengjun and Du, Li and Zhou, Pingkun and Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn},
abstractNote = {Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} 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 β-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 β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-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 β-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 β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.},
doi = {10.1016/J.IJROBP.2015.05.043},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 93,
place = {United States},
year = {2015},
month = {10}
}