A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells
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.
Key Biomarkers
Cited By (7)
- Transforming growth factor-beta: recent advances on its role in immune toleranceMethods in molecular biology · 2011
- All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg/Th17 profile in human ulcerative and murine colitisJournal of Leukocyte Biology · 2009
- From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokinesNature Immunology · 2012
- Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?Nature reviews. Immunology · 2009
- SHIP regulates the reciprocal development of T regulatory and Th17 cellsThe Journal of Immunology · 2009
- Control of regulatory T cell lineage commitment and maintenanceImmunity · 2009
- Foxp3+ regulatory T cells: differentiation, specification, subphenotypesNature Immunology · 2009
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