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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Luo, X; Zhang, Q; Liu, V; Xia, Z; Pothoven, KL; Lee, C

Published Date

  • March 1, 2008

Published In

Volume / Issue

  • 180 / 5

Start / End Page

  • 2757 - 2761

PubMed ID

  • 18292494

Pubmed Central ID

  • PMC4289405

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.180.5.2757


  • eng

Conference Location

  • United States