CD4(+) CD25(+) regulatory cells are a subpopulation of T lymphoiytes 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 Toxp3 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-9 and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxy3-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 Toxp3 and a positive autoregulatory loop of TGF-beta signaling due to the absence of Smad7.

Fantini, M.c., Becker, C., Monteleone, G., Pallone, F., Galle, P.r., Neurath, M.f. (2004). Cutting edge: TGF-beta induces a regulatory phenotype in CD4(+)CD25(-) T cells through Foxp3 induction and down-regulation of Smad7. JOURNAL OF IMMUNOLOGY, 172(9), 5149-5153.

Cutting edge: TGF-beta induces a regulatory phenotype in CD4(+)CD25(-) T cells through Foxp3 induction and down-regulation of Smad7

FANTINI, MASSIMO CLAUDIO;MONTELEONE, GIOVANNI;PALLONE, FRANCESCO;
2004-01-01

Abstract

CD4(+) CD25(+) regulatory cells are a subpopulation of T lymphoiytes 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 Toxp3 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-9 and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxy3-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 Toxp3 and a positive autoregulatory loop of TGF-beta signaling due to the absence of Smad7.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - Gastroenterologia
English
CD4 antigen; interleukin 2 receptor; Smad3 protein; Smad4 protein; Smad7 protein; transcription factor; transcription factor FoxP3; transforming growth factor beta; unclassified drug; animal cell; article; autoregulation; controlled study; down regulation; flow cytometry; immunological tolerance; lymphocyte clone; lymphocyte function; lymphocyte proliferation; mouse; nonhuman; phenotype; priority journal; protein expression; protein function; protein induction; regulatory mechanism; signal transduction; T lymphocyte; T lymphocyte subpopulation; thymus; transcription regulation; Western blotting; Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Cells, Cultured; DNA-Binding Proteins; Down-Regulation; Forkhead Transcription Factors; Humans; Immunophenotyping; Mice; Receptors, Interleukin-2; Signal Transduction; Smad7 Protein; Spleen; T-Lymphocyte Subsets; Thymus Gland; Trans-Activators; Transforming Growth Factor beta
Fantini, M.c., Becker, C., Monteleone, G., Pallone, F., Galle, P.r., Neurath, M.f. (2004). Cutting edge: TGF-beta induces a regulatory phenotype in CD4(+)CD25(-) T cells through Foxp3 induction and down-regulation of Smad7. JOURNAL OF IMMUNOLOGY, 172(9), 5149-5153.
Fantini, Mc; Becker, C; Monteleone, G; Pallone, F; Galle, Pr; Neurath, Mf
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/40787
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