A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells
Top Cited Papers
- 27 April 2008
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 9 (6) , 632-640
- https://doi.org/10.1038/ni.1607
Abstract
The molecular mechanisms directing the development of 'natural' CD4+CD25+Foxp3+ regulatory T cells (T(reg) cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor-beta receptor I (TbetaRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes at postnatal days 3-5. Paradoxically, however, beginning 1 week after birth, the same TbetaRI-mutant mice showed accelerated expansion of thymic CD4+CD25+Foxp3+ populations. This rapid recovery of Foxp3+ thymocytes was attributable mainly to overproduction of and heightened responsiveness to interleukin 2, as genetic ablation of interleukin 2 in TbetaRI-mutant mice resulted in a complete absence of CD4+CD25+Foxp3+ cells from the thymus and periphery. Thus, transforming growth factor-beta signaling is critical to the thymic development of natural CD4+CD25+Foxp3+ T(reg) cells.Keywords
This publication has 52 references indexed in Scilit:
- Treg cells: guardians for lifeNature Immunology, 2007
- Nonredundant roles for Stat5a/b in directly regulating Foxp3Blood, 2007
- Transforming Growth Factor-β Controls Development, Homeostasis, and Tolerance of T Cells by Regulatory T Cell-Dependent and -Independent MechanismsImmunity, 2006
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006
- TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cellsThe Journal of Experimental Medicine, 2005
- Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3 The Journal of Experimental Medicine, 2003
- Mechanisms of TGF-β Signaling from Cell Membrane to the NucleusCell, 2003
- Natural versus adaptive regulatory T cellsNature Reviews Immunology, 2003
- Maternal Rescue of Transforming Growth Factor-β 1 Null MiceScience, 1994
- Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory diseaseNature, 1992