RT Journal Article
SR Electronic
T1 IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3<sup>+</sup> Regulatory T Cells
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 280
OP 290
DO 10.4049/jimmunol.178.1.280
VO 178
IS 1
A1 Burchill, Matthew A.
A1 Yang, Jianying
A1 Vogtenhuber, Christine
A1 Blazar, Bruce R.
A1 Farrar, Michael A.
YR 2007
UL http://www.jimmunol.org/content/178/1/280.abstract
AB IL-2−/− mice develop autoimmunity despite having relatively normal numbers of regulatory T cells (Tregs). In contrast, we demonstrate that IL-2−/− × IL-15−/− and IL-2Rβ−/− mice have a significant decrease in Treg numbers. Ectopic expression of foxp3 in a subset of CD4+ T cells rescued Treg development and prevented autoimmunity in IL-2Rβ−/− mice, suggesting that IL-2Rβ-dependent signals regulate foxp3 expression in Tregs. Subsequent analysis of IL-2Rβ-dependent signal transduction pathways established that the transcription factor STAT5 is necessary and sufficient for Treg development. Specifically, T cell-specific deletion of STAT5 prevented Treg development; conversely, reconstitution of IL-2Rβ−/− mice with bone marrow cells expressing an IL-2Rβ mutant that exclusively activates STAT5 restored Treg development. Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rβ-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3.