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

Authors :
Luo X
Zhang Q
Liu V
Xia Z
Pothoven KL
Lee C
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Mar 01; Vol. 180 (5), pp. 2757-61.
Publication Year :
2008

Abstract

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.

Details

Language :
English
ISSN :
0022-1767
Volume :
180
Issue :
5
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
18292494
Full Text :
https://doi.org/10.4049/jimmunol.180.5.2757