IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3+ Regulatory T Cells
University of Minnesota · University of Minnesota Medical Center · +1 more institution
Abstract
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…
Citation impact
- FWCI
- 18.48
- Percentile
- 100%
- References
- 40
Authors
5- MAMatthew A. BurchillCorresponding
University of Minnesota, University of Minnesota Medical Center, Center for Cancer Research
- JYJianying Yang
University of Minnesota, University of Minnesota Medical Center, Center for Cancer Research
- CVChristine Vogtenhuber
University of Minnesota, University of Minnesota Medical Center
- BRBruce R. Blazar
University of Minnesota, University of Minnesota Medical Center
- MAMichael A. Farrar
University of Minnesota, University of Minnesota Medical Center, Center for Cancer Research
Topics & keywords
- STAT5
- FOXP3
- Autoimmunity
- Biology
- Cell biology
- Ectopic expression
- Signal transduction
- Immunology