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Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.

Publication ,  Journal Article
Luo, X; Zhang, Q; Liu, V; Xia, Z; Pothoven, KL; Lee, C
Published in: J Immunol
March 1, 2008

The peripheral induction of T regulatory cells can be accomplished by TGF-beta through an epigenetic regulation leading to the expression of Foxp3. However, the exact mechanism of such a TGF-beta-mediated action remains unclear. In the current study, we found that TGF-beta treatment of CD4+CD25- T cells during T cell activation led to a transient inhibition of the phosphorylation of ERK followed by the induction of Foxp3 expression in these cells. Direct treatment with a specific ERK inhibitor, UO126, during CD4+CD25- T cell activation also induced Foxp3 expression and conferred a suppressive function to the induced Foxp3+ T cells. Furthermore, treatment of T cells with either TGF-beta or UO126 significantly down-regulated the expression of DNMTs, a reaction normally elicited by demethylation agents, such as 5-Aza-2'-deoxycytidine. These results indicate that the epigenetic regulation of TGF-beta-induced expression of Foxp3 may be mediated through the inactivation of ERK.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

March 1, 2008

Volume

180

Issue

5

Start / End Page

2757 / 2761

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes, Regulatory
  • Resting Phase, Cell Cycle
  • Receptors, Antigen, T-Cell
  • Phosphorylation
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Mice, Transgenic
  • Mice, Inbred NOD
  • Mice, Inbred BALB C
 

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Luo, X., Zhang, Q., Liu, V., Xia, Z., Pothoven, K. L., & Lee, C. (2008). Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK. J Immunol, 180(5), 2757–2761. https://doi.org/10.4049/jimmunol.180.5.2757
Luo, Xunrong, Qiang Zhang, Victoria Liu, Zhenbiao Xia, Kathryn L. Pothoven, and Chung Lee. “Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.J Immunol 180, no. 5 (March 1, 2008): 2757–61. https://doi.org/10.4049/jimmunol.180.5.2757.
Luo X, Zhang Q, Liu V, Xia Z, Pothoven KL, Lee C. Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK. J Immunol. 2008 Mar 1;180(5):2757–61.
Luo, Xunrong, et al. “Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.J Immunol, vol. 180, no. 5, Mar. 2008, pp. 2757–61. Pubmed, doi:10.4049/jimmunol.180.5.2757.
Luo X, Zhang Q, Liu V, Xia Z, Pothoven KL, Lee C. Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK. J Immunol. 2008 Mar 1;180(5):2757–2761.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

March 1, 2008

Volume

180

Issue

5

Start / End Page

2757 / 2761

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • T-Lymphocytes, Regulatory
  • Resting Phase, Cell Cycle
  • Receptors, Antigen, T-Cell
  • Phosphorylation
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Mice, Transgenic
  • Mice, Inbred NOD
  • Mice, Inbred BALB C