A critical function for TGF-beta 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.
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Nature Immunology, Nature Publishing Group, 2008, 9 (6), pp.632-40. 〈10.1038/ni.1607〉
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Soumis le : mardi 18 mai 2010 - 07:57:39
Dernière modification le : jeudi 15 février 2018 - 08:48:14

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Yongzhong Liu, Pin Zhang, Jun Li, Ashok Kulkarni, Sylvain Perruche, et al.. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.. Nature Immunology, Nature Publishing Group, 2008, 9 (6), pp.632-40. 〈10.1038/ni.1607〉. 〈inserm-00484154〉

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