Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.
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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- 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
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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