Foxo proteins cooperatively control the differentiation of Foxp3 + regulatory T cells Journal Article
| Authors: | Ouyang, W.; Beckett, O.; Ma, Q.; Paik, J. H.; DePinho, R. A.; Li, M. O. |
| Article Title: | Foxo proteins cooperatively control the differentiation of Foxp3 + regulatory T cells |
| Abstract: | CD4+ regulatory T cells (Treg cells) characterized by expression of the transcription factor Foxp3 have a pivotal role in maintaining immunological tolerance. Here we show that mice with T cell-specific deletion of both the Foxo1 and Foxo3 transcription factors (collectively called 'Foxo proteins' here) developed a fatal multifocal inflammatory disorder due in part to Treg cell defects. Foxo proteins functioned in a Treg cell-intrinsic manner to regulate thymic and transforming growth factor-Β (TGF-Β)-induced Foxp3 expression, in line with the ability of Foxo proteins to bind to Foxp3 locus and control Foxp3 promoter activity. Transcriptome analyses showed that Foxo proteins regulated the expression of additional T reg cell-associated genes and were essential for inhibiting the acquisition of effector T cell characteristics by Treg cells. Thus, Foxo proteins have crucial roles in specifying the Treg cell lineage. © 2010 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; protein expression; promoter region; mutation; nonhuman; protein function; transcription factor foxp3; forkhead transcription factors; animal cell; mouse; animals; mice; mice, knockout; cells, cultured; gene expression profiling; transforming growth factor beta; protein depletion; animal experiment; inflammation; mice, mutant strains; protein binding; gene locus; cell differentiation; cell lineage; gene expression regulation, developmental; lymphocyte differentiation; regulatory t lymphocyte; regulatory mechanism; t-lymphocytes, regulatory; thymus gland; growth regulation; gene control; effector cell; antigens, cd4; transcriptome; immunopathology; transcription factor fkhrl1; transcription factor fkhr; gene activity; inflammatory disease; transcription factor foxo; regulatory elements, transcriptional |
| Journal Title: | Nature Immunology |
| Volume: | 11 |
| Issue: | 7 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-07-01 |
| Start Page: | 618 |
| End Page: | 627 |
| Language: | English |
| DOI: | 10.1038/ni.1884 |
| PUBMED: | 20467422 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 14" - "Export Date: 20 April 2011" - "CODEN: NIAMC" - "Source: Scopus" |
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