| First Author | Burchill MA | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 1 | Pages | 280-90 |
| PubMed ID | 17182565 | Mgi Jnum | J:141932 |
| Mgi Id | MGI:3820038 | Doi | 10.4049/jimmunol.178.1.280 |
| Citation | Burchill MA, et al. (2007) IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol 178(1):280-90 |
| abstractText | IL-2(-/-) mice develop autoimmunity despite having relatively normal numbers of regulatory T cells (Tregs). In contrast, we demonstrate that IL-2(-/-) x IL-15(-/-) and IL-2Rbeta(-/-) 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-2Rbeta(-/-) mice, suggesting that IL-2Rbeta-dependent signals regulate foxp3 expression in Tregs. Subsequent analysis of IL-2Rbeta-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-2Rbeta(-/-) mice with bone marrow cells expressing an IL-2Rbeta mutant that exclusively activates STAT5 restored Treg development. Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3. |
