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Int J Clin Exp Pathol 2012;5(7):626-633
Original Article
Synergy between IL-6 and TGF-β signaling promotes FOXP3 degradation
Zhimei Gao, Yayi Gao, Zhiyuan Li, Zuojia Chen, Daru Lu, Andy Tsun, Bin Li
The Bioengineering Graduate Program, School of Life Sciences, Fudan University, Shanghai, 200433, China; Key Laboratory of Molecular
Virology & Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, 411 Hefei Road (South), Shanghai, 200025, China
Received July 23, 2012; Accepted August 5, 2012; Epub September 5, 2012; Published September 15, 2012
Abstract: The forkhead family transcription factor FOXP3 is critical for the differentiation and function of CD4+ CD25+ regulatory T cells (Treg).
How FOXP3 protein level is negatively regulated under the inflammatory microenvironment is largely unknown. Here we report that the
combination of transforming growth factor-beta (TGF-β) and IL-6 treatment (IL-6/TGF-β) can synergistically downregulate FOXP3 at the
posttranslational level by promoting FOXP3 protein degradation. In our FOXP3 overexpression model, we found that IL-6/TGF-β treatment
upregulated IL-6R expression but did not affect the stability of FOXP3 mRNA. Moreover, we found that the proteasome inhibitor MG132 could
inhibit IL-6/TGF-β-mediated downregulation of FOXP3 protein, which reveals a potential pathway for modulating Treg activity by preventing
FOXP3 degradation during inflammation. (IJCEP1207019)
Keywords: FOXP3, Treg, instability, IL-6, TGF-β, proteasome
Address all correspondence to:
Andy Tsun, PhD and Bin Li, PhD
Key Laboratory of Molecular Virology & Immunology
Unit of Molecular Immunology
Institut Pasteur of Shanghai
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
411 Hefei Road (South), Shanghai, 200025, China.
E-mail: andy@sibs.ac.cn; Or: E-mail: binli@sibs.ac.cn
Original Article
Synergy between IL-6 and TGF-β signaling promotes FOXP3 degradation
Zhimei Gao, Yayi Gao, Zhiyuan Li, Zuojia Chen, Daru Lu, Andy Tsun, Bin Li
The Bioengineering Graduate Program, School of Life Sciences, Fudan University, Shanghai, 200433, China; Key Laboratory of Molecular
Virology & Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, 411 Hefei Road (South), Shanghai, 200025, China
Received July 23, 2012; Accepted August 5, 2012; Epub September 5, 2012; Published September 15, 2012
Abstract: The forkhead family transcription factor FOXP3 is critical for the differentiation and function of CD4+ CD25+ regulatory T cells (Treg).
How FOXP3 protein level is negatively regulated under the inflammatory microenvironment is largely unknown. Here we report that the
combination of transforming growth factor-beta (TGF-β) and IL-6 treatment (IL-6/TGF-β) can synergistically downregulate FOXP3 at the
posttranslational level by promoting FOXP3 protein degradation. In our FOXP3 overexpression model, we found that IL-6/TGF-β treatment
upregulated IL-6R expression but did not affect the stability of FOXP3 mRNA. Moreover, we found that the proteasome inhibitor MG132 could
inhibit IL-6/TGF-β-mediated downregulation of FOXP3 protein, which reveals a potential pathway for modulating Treg activity by preventing
FOXP3 degradation during inflammation. (IJCEP1207019)
Keywords: FOXP3, Treg, instability, IL-6, TGF-β, proteasome
Address all correspondence to:
Andy Tsun, PhD and Bin Li, PhD
Key Laboratory of Molecular Virology & Immunology
Unit of Molecular Immunology
Institut Pasteur of Shanghai
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
411 Hefei Road (South), Shanghai, 200025, China.
E-mail: andy@sibs.ac.cn; Or: E-mail: binli@sibs.ac.cn
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