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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 Treg

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

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ACCESSIONS GENE EXPRESSION OMNIBUS * GSE21678 CHANGE HISTORY * _ 18 MAY 2010 In the version of this article initially published online, the final sentence of the “Chromatin

immunoprecipitation” paragraph of the Online Methods section was incorrect. The correct sentence is “Primers for analysis of the binding of Foxo1 and Foxo3 to the Foxp3 locus are in

Supplementary Table 5.” The error has been corrected for the PDF and HTML versions of this article. _ * _ 18 MAY 2010 In the version of this supplementary file originally posted online, the

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(2009). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank R. Flavell (Yale University) for the Foxp3-RFP mouse strain; S. Ghosh (Columbia

University) for luciferase reporter constructs; A. Brunet (Stanford University) for the Foxo3-specific antibody; and A. Rudensky, M. Huse and Y. Zheng for discussions. Supported by the Starr

Cancer Consortium (13-A123 to M.O.L.), the National Institute of Arthritis, Musculoskeletal and Skin Diseases (K01 AR053595 to M.O.L.), the Arthritis Foundation (M.O.L.), the Robert A. and

Renee E. Belfer Family Foundation (R.A.D.), the Damon-Runyon Cancer Research Foundation (J.-h.P.) and the Rita Allen Foundation (M.O.L.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA Weiming Ouyang, Omar Beckett, Qian Ma & Ming O Li * Department of Medical Oncology, Department of

Medicine and Department of Genetics, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA Ji-hye Paik & Ronald A

DePinho Authors * Weiming Ouyang View author publications You can also search for this author inPubMed Google Scholar * Omar Beckett View author publications You can also search for this

author inPubMed Google Scholar * Qian Ma View author publications You can also search for this author inPubMed Google Scholar * Ji-hye Paik View author publications You can also search for

this author inPubMed Google Scholar * Ronald A DePinho View author publications You can also search for this author inPubMed Google Scholar * Ming O Li View author publications You can also

search for this author inPubMed Google Scholar CONTRIBUTIONS W.O. and M.O.L. designed the research and analyzed the data; W.O., O.B. and Q.M. did experiments; R.A.D. and J.-h.P. provided the

mouse strain with floxed _Foxo3_ and feedback on the manuscript; and W.O. and M.O.L. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Ming O Li. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–14, Tables 1–5 (PDF 3660 kb) RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ouyang, W., Beckett, O., Ma, Q. _et al._ Foxo proteins cooperatively control the differentiation of Foxp3+

regulatory T cells. _Nat Immunol_ 11, 618–627 (2010). https://doi.org/10.1038/ni.1884 Download citation * Received: 08 March 2010 * Accepted: 07 May 2010 * Published: 13 May 2010 * Issue

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