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E3 Ubiquitin Ligase Cbl-b Regulates Thymic-Derived CD4+CD25+ Regulatory T Cell Development by Targeting Foxp3 for Ubiquitination.
- Source :
-
Journal of Immunology . 2/15/2015, Vol. 194 Issue 4, p1639-1645. 7p. - Publication Year :
- 2015
-
Abstract
- CD28 costimulation is essential for the development of thymic-derived CD4+CD25+Foxp3+ regulatory T cells ("tTregs"). E3 ubiquitin ligase Cbl-b has been shown to regulate CD28 dependence of T cell activation. In this paper, we report that the loss of Cbl-b partially but significantly rescues the defective development of tTregs in Cd28-/- mice. This partial rescue is independent of IL-2. Mechanistically, Cbl-b binds to Foxp3 upon TCR stimulation and, together with Stubl, targets Foxp3 for ubiquitination and subsequently degradation in the proteasome. As Cbl-b self-ubiquitination and proteasomal degradation is impaired in Cd28-/- T cells, the defective development of tTregs in Cd28-/- mice may in part be due to increased Foxp3 ubiquitination and degradation targeted by Stubl and Cbl-b. Treating Cd28-/- mice with a proteasome inhibitor completely rescues defective tTreg development in these mice. Therefore, Cbl-b, together with Stubl, ubiquitinate Foxp3, and regulate tTreg development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 194
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103556300
- Full Text :
- https://doi.org/10.4049/jimmunol.1402434