A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.
Fiche publication
Date publication
juin 2008
Journal
Nature immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PERRUCHE Sylvain
Tous les auteurs :
Liu Y, Zhang P, Li J, Kulkarni AB, Perruche S, Chen W
Lien Pubmed
Résumé
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.
Mots clés
Animals, B-Cell Activating Factor, metabolism, CD4-Positive T-Lymphocytes, metabolism, Forkhead Transcription Factors, analysis, Gene Expression Regulation, drug effects, Mice, Signal Transduction, physiology, T-Lymphocytes, Regulatory, classification, Transforming Growth Factor beta, metabolism
Référence
Nat. Immunol.. 2008 Jun;9(6):632-40