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

被引:928
作者
Fantini, MC
Becker, C
Monteleone, G
Pallone, F
Galle, PR
Neurath, MF
机构
[1] Johannes Gutenberg Univ Mainz, Immunol Lab, Med Clin 1, D-55131 Mainz, Germany
[2] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy
关键词
D O I
10.4049/jimmunol.172.9.5149
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:5149 / 5153
页数:5
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