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PMID: 19767756 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells.

Nature immunology ·Vol. 10 ·No. 11 ·2009-11-00 ·Pages 1170-7

Rudra D, Egawa T, Chong MM, Treuting P, Littman DR, Rudensky AY

Abstract

The transcription factor Foxp3 has an indispensable role in establishing stable transcriptional and functional programs of regulatory T cells (T(reg) cells). Loss of Foxp3 expression in mature T(reg) cells results in a failure of suppressor function, yet the molecular mechanisms that ensure steady, heritable Foxp3 expression in the T(reg) cell lineage remain unknown. Using T(reg) cell-specific gene targeting, we found that complexes of the transcription factors Runx and CBFbeta were required for maintenance of Foxp3 mRNA and protein expression in T(reg) cells. Consequently, mice lacking CBFbetab exclusively in the T(reg) cell lineage had a moderate lymphoproliferative syndrome. Thus, Runx-CBFbeta complexes maintain stable high expression of Foxp3 and serve as an essential determinant of T(reg) cell lineage stability.

MeSH Terms
Adoptive Transfer Animals Bone Marrow Transplantation Cell Lineage/immunology Core Binding Factor beta Subunit/immunology,metabolism Female Forkhead Transcription Factors/immunology,metabolism Gene Expression Regulation Gene Targeting Lymph Nodes/cytology,immunology,pathology Lymphoproliferative Disorders/immunology,pathology Male Mice Mice, Inbred C57BL Spleen/cytology,immunology,pathology T-Lymphocytes, Regulatory/immunology,metabolism Thymus Gland/cytology,immunology
Chemicals
Cbfb protein, mouse Core Binding Factor beta Subunit Forkhead Transcription Factors Foxp3 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rudra Dipayan
Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Egawa Takeshi
Chong Mark M W
Treuting Piper
Littman Dan R
Rudensky Alexander Y
References (34)
34 references, click to expand
  1. Absence of T cells confers increased pulmonary arterial hypertension and vascular remodeling.
    Am J Respir Crit Care Med. 2007 Jun 15;175(12):1280-9 PMID: 17413127
  2. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
    Nat Immunol. 2003 Apr;4(4):330-6 PMID: 12612578
  3. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells.
    J Immunol. 2007 Jan 1;178(1):280-90 PMID: 17182565
  4. Autoimmunity and pulmonary hypertension: a perspective.
    Eur Respir J. 2005 Dec;26(6):1110-8 PMID: 16319344
  5. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors.
    Mol Cell Biol. 1994 Jan;14(1):473-83 PMID: 8264615
  6. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta.
    Cell. 2001 Mar 9;104(5):755-67 PMID: 11257229
  7. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression.
    Nature. 2007 Feb 15;445(7129):766-70 PMID: 17220876
  8. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors.
    Immunity. 2004 Aug;21(2):267-77 PMID: 15308106
  9. Nonredundant roles for Stat5a/b in directly regulating Foxp3.
    Blood. 2007 May 15;109(10):4368-75 PMID: 17227828
  10. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development.
    Cell. 2002 Nov 27;111(5):621-33 PMID: 12464175
  11. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces.
    Immunity. 2008 Apr;28(4):546-58 PMID: 18387831
  12. FOXP3 controls regulatory T cell function through cooperation with NFAT.
    Cell. 2006 Jul 28;126(2):375-87 PMID: 16873067
  13. Epigenetic gene silencing by Runx proteins.
    Oncogene. 2004 May 24;23(24):4341-5 PMID: 15156191
  14. An essential role for Scurfin in CD4+CD25+ T regulatory cells.
    Nat Immunol. 2003 Apr;4(4):337-42 PMID: 12612581
  15. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells.
    Nature. 2007 Feb 22;445(7130):936-40 PMID: 17237761
  16. Control of regulatory T cell development by the transcription factor Foxp3.
    Science. 2003 Feb 14;299(5609):1057-61 PMID: 12522256
  17. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation.
    J Exp Med. 2007 Jul 9;204(7):1543-51 PMID: 17591856
  18. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer.
    Nat Immunol. 2008 Feb;9(2):194-202 PMID: 18157133
  19. c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor delta enhancer.
    Mol Cell Biol. 1995 Jun;15(6):3090-9 PMID: 7760805
  20. Regulatory T cells and immune tolerance.
    Cell. 2008 May 30;133(5):775-87 PMID: 18510923
  21. Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions.
    Genes Dev. 1995 Apr 15;9(8):995-1008 PMID: 7774816
  22. Foxp3 occupancy and regulation of key target genes during T-cell stimulation.
    Nature. 2007 Feb 22;445(7130):931-5 PMID: 17237765
  23. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation.
    EMBO J. 2001 Feb 15;20(4):723-33 PMID: 11179217
  24. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3.
    Nat Immunol. 2007 Mar;8(3):277-84 PMID: 17220892
  25. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1.
    Nature. 2007 Apr 5;446(7136):685-9 PMID: 17377532
  26. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice.
    Nat Immunol. 2007 Feb;8(2):191-7 PMID: 17136045
  27. Regulatory T cell development in the absence of functional Foxp3.
    Nat Immunol. 2007 Apr;8(4):359-68 PMID: 17273171
  28. Foxp3-dependent programme of regulatory T-cell differentiation.
    Nature. 2007 Feb 15;445(7129):771-5 PMID: 17220874
  29. Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
    Nat Immunol. 2007 Feb;8(2):145-53 PMID: 17195845
  30. Pulmonary arterial remodeling induced by a Th2 immune response.
    J Exp Med. 2008 Feb 18;205(2):361-72 PMID: 18227220
  31. Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins.
    J Virol. 1995 Aug;69(8):4941-9 PMID: 7609063
  32. Core binding factor and its role in normal hematopoietic development.
    Curr Opin Hematol. 2001 Jul;8(4):192-6 PMID: 11561154
  33. Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer.
    J Exp Med. 2007 Aug 6;204(8):1749-55 PMID: 17646405
  34. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1795
Published
2009-11-00
Epub
2009-00-20
Pages
1170-7
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2764816
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R01 AI061816 · United States
NIAID NIH HHS · R01 AI061816-05 · United States
NIAID NIH HHS · R37 AI034206 · United States
External Links
PubMed source DOI: 10.1038/ni.1795 PMC Full Text View journal details
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