IL-2 receptor β-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells

Matthew A. Burchill, Jianying Yang, Christine Vogtenhuber, Bruce R. Blazar, Michael A. Farrar

Research output: Contribution to journalArticle

515 Scopus citations

Abstract

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-depedent 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-dependeat STAT5 activation promotes Treg differentiation by regulating expression of foxp3.

Original languageEnglish (US)
Pages (from-to)280-290
Number of pages11
JournalJournal of Immunology
Volume178
Issue number1
DOIs
StatePublished - Jan 1 2007

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