Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells
Copyright policy )Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells
The transcription factor Foxp3 is essential for optimal regulatory T (T reg) cell development and function. Here, we show that CD4+ T cells from Cbl-b RING finger mutant knockin or Cbl-b–deficient mice show impaired TGF-β–induced Foxp3 expression. These T cells display augmented Foxo3a phosphorylation, but normal TGF-β signaling. Expression of Foxo3a rescues Foxp3 expression in Cbl-b–deficient T cells, and Foxo3a deficiency results in defective TGF-β–driven Foxp3 induction. A Foxo3a-binding motif is present in a proximal region of the Foxp3 promoter, and is required for Foxo3a association. Foxo1 exerts similar effects as Foxo3a on Foxp3 expression. This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation.
- Harvard Medical School United States
- Dana-Farber Cancer Institute United States
- La Jolla Institute For Allergy & Immunology United States
- Dana Farber Cancer Institute Harvard Medical School United States
- Harvard University United States
Forkhead Box Protein O1, Forkhead Box Protein O3, 610, Cell Differentiation, Forkhead Transcription Factors, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, Mice, Inbred C57BL, Jurkat Cells, Mice, Gene Expression Regulation, Animals, Humans, Proto-Oncogene Proteins c-cbl, Promoter Regions, Genetic, Adaptor Proteins, Signal Transducing, Protein Binding, Signal Transduction
Forkhead Box Protein O1, Forkhead Box Protein O3, 610, Cell Differentiation, Forkhead Transcription Factors, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, Mice, Inbred C57BL, Jurkat Cells, Mice, Gene Expression Regulation, Animals, Humans, Proto-Oncogene Proteins c-cbl, Promoter Regions, Genetic, Adaptor Proteins, Signal Transducing, Protein Binding, Signal Transduction
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