Cutting Edge: TGF-β-Induced Expression of Foxp3 in T cells Is Mediated through Inactivation of ERK
| Autor: | Victoria Liu, Chung Lee, Kathryn L. Pothoven, Xunrong Luo, Qiang Zhang, Zhenbiao Xia |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
MAPK/ERK pathway T cell Immunology Receptors Antigen T-Cell Down-Regulation Mice Transgenic Biology Resting Phase Cell Cycle T-Lymphocytes Regulatory Article DNA Methyltransferase 3A Transforming Growth Factor beta1 Mice Antigen Mice Inbred NOD medicine Animals Immunology and Allergy DNA (Cytosine-5-)-Methyltransferases IL-2 receptor Phosphorylation Cells Cultured Mitogen-Activated Protein Kinase 1 Regulation of gene expression Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 ZAP70 FOXP3 Forkhead Transcription Factors DNA Methylation Molecular biology Enzyme Activation medicine.anatomical_structure Gene Expression Regulation DNA methylation |
| Zdroj: | The Journal of Immunology. 180:2757-2761 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.180.5.2757 |
| Popis: | The peripheral induction of T regulatory cells can be accomplished by TGF-β through an epigenetic regulation leading to the expression of Foxp3. However, the exact mechanism of such a TGF-β-mediated action remains unclear. In the current study, we found that TGF-β 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-β 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-β-induced expression of Foxp3 may be mediated through the inactivation of ERK. |
| Databáze: | OpenAIRE |
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