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PMID:15100250
| Citation |
Fantini, MC, Becker, C, Monteleone, G, Pallone, F, Galle, PR and Neurath, MF (2004) Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172:5149-53 |
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| Abstract |
CD4(+)CD25(+) regulatory cells are a subpopulation of T lymphocytes of thymic origin. However, recent data suggest an alternative commitment of regulatory T cells in the periphery, although the precise mechanism is unknown. In the present work, we demonstrate that TGF-beta is able to induce Foxp3 expression and subsequently a regulatory phenotype in CD4(+)CD25(-) peripheral murine T cells. Similarly, TGF-beta induced Foxp3 in human CD4(+)CD25(-) T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF-beta and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxp3-mediated down-regulation of Smad7 subsequently rendered CD4(+)CD25(-) T cells highly susceptible to the morphogenic and regulatory effects of TGF-beta signaling via Smad3/4. In summary, we demonstrate that TGF-beta induces a regulatory phenotype in CD4(+)CD25(-) T cells through the induction of Foxp3 and a positive autoregulatory loop of TGF-beta signaling due to the absence of Smad7. |
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| Keywords |
Animals; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; Cell Differentiation/immunology; Cells, Cultured; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/physiology; Down-Regulation/immunology; Forkhead Transcription Factors; Humans; Immunophenotyping; Mice; Receptors, Interleukin-2/metabolism; Signal Transduction/immunology; Smad7 Protein; Spleen/cytology; Spleen/immunology; T-Lymphocyte Subsets/cytology; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; Thymus Gland/cytology; Thymus Gland/immunology; Trans-Activators/antagonists & inhibitors; Trans-Activators/physiology; Transforming Growth Factor beta/antagonists & inhibitors; Transforming Growth Factor beta/biosynthesis; Transforming Growth Factor beta/physiology |
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Significance
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