| Title | Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Harada Y, Harada Y, Elly C, Ying G, Paik J-H, DePinho RA, Liu Y-C |
| Journal | J Exp Med |
| Volume | 207 |
| Issue | 7 |
| Pagination | 1381-91 |
| Date Published | 2010 Jul 05 |
| ISSN | 1540-9538 |
| Keywords | Adaptor Proteins, Signal Transducing, Animals, Cell Differentiation, Forkhead Box Protein O1, Forkhead Box Protein O3, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Jurkat Cells, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-cbl, Signal Transduction, T-Lymphocytes, Regulatory |
| Abstract | 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-beta-induced Foxp3 expression. These T cells display augmented Foxo3a phosphorylation, but normal TGF-beta signaling. Expression of Foxo3a rescues Foxp3 expression in Cbl-b-deficient T cells, and Foxo3a deficiency results in defective TGF-beta-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. |
| DOI | 10.1084/jem.20100004 |
| Alternate Journal | J Exp Med |
| PubMed ID | 20439537 |
Related Faculty:
Ji-Hye Paik, Ph.D.