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Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.
- 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.
- Subjects :
- Animals
Cells, Cultured
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors
DNA (Cytosine-5-)-Methyltransferases biosynthesis
DNA Methylation
DNA Methyltransferase 3A
Down-Regulation genetics
Down-Regulation immunology
Enzyme Activation immunology
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, Transgenic
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Phosphorylation
Receptors, Antigen, T-Cell physiology
Resting Phase, Cell Cycle immunology
T-Lymphocytes, Regulatory enzymology
DNA Methyltransferase 3B
Forkhead Transcription Factors biosynthesis
Gene Expression Regulation immunology
Mitogen-Activated Protein Kinase 1 antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 antagonists & inhibitors
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Transforming Growth Factor beta1 physiology
Subjects
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