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PMID: 22133865 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

T-bet employs diverse regulatory mechanisms to repress transcription.

Trends in immunology ·Vol. 33 ·No. 2 ·2012-02-00 ·Pages 78-83

Oestreich KJ, Weinmann AS

Abstract

Lineage-defining transcription factors are responsible for activating the signature genes required for a given cell fate. They are also needed to repress the genetic programs associated with alternative lineage decisions. The T-box transcription factor T-bet is required for CD4(+) T helper 1 (Th1) cell differentiation. Numerous studies have explored the mechanisms by which T-bet activates the Th1 gene profile, but until recently not much was known about the mechanisms that T-bet utilizes to negatively regulate alternative T helper cell differentiation pathways such as the Th2 and Th17 fates. Here, we discuss new advances in the field that highlight the diverse mechanisms that T-bet employs to antagonize the gene programs for alternative T helper cell fates.

MeSH Terms
Animals CD8-Positive T-Lymphocytes/immunology Cell Differentiation Cell Lineage Humans Receptors, Antigen, T-Cell/immunology T-Box Domain Proteins/immunology T-Lymphocytes, Helper-Inducer/cytology,immunology
Chemicals
Receptors, Antigen, T-Cell T-Box Domain Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Oestreich Kenneth J
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Weinmann Amy S
References (42)
42 references, click to expand
  1. The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
    J Exp Med. 2011 May 9;208(5):1001-13 PMID: 21518797
  2. Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression.
    Genes Dev. 2008 Nov 1;22(21):2980-93 PMID: 18981476
  3. T-bet in disease.
    Nat Immunol. 2011 Jun 20;12(7):597-606 PMID: 21685955
  4. Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection.
    Immunity. 2007 Sep;27(3):393-405 PMID: 17892848
  5. Regulation of interferon-gamma during innate and adaptive immune responses.
    Adv Immunol. 2007;96:41-101 PMID: 17981204
  6. BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor.
    Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6947-52 PMID: 8692924
  7. How are T(H)1 and T(H)2 effector cells made?
    Curr Opin Immunol. 2009 Apr;21(2):153-60 PMID: 19375293
  8. T-bet's ability to regulate individual target genes requires the conserved T-box domain to recruit histone methyltransferase activity and a separate family member-specific transactivation domain.
    Mol Cell Biol. 2007 Dec;27(24):8510-21 PMID: 17923685
  9. Identification of cooperative monomeric Brachyury sites conferring T-bet responsiveness to the proximal IFN-gamma promoter.
    Int Immunol. 2003 Oct;15(10):1149-60 PMID: 13679385
  10. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt.
    Nat Immunol. 2011 Jan;12(1):96-104 PMID: 21151104
  11. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3.
    Science. 2005 Jan 21;307(5708):430-3 PMID: 15662016
  12. Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.
    Mol Cell. 2010 Nov 24;40(4):594-605 PMID: 21095589
  13. A mechanism underlying STAT4-mediated up-regulation of IFN-gamma induction inTCR-triggered T cells.
    Int Immunol. 2004 Feb;16(2):295-302 PMID: 14734615
  14. Bcl6 mediates the development of T follicular helper cells.
    Science. 2009 Aug 21;325(5943):1001-5 PMID: 19628815
  15. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.
    Nat Immunol. 2005 Dec;6(12):1236-44 PMID: 16273099
  16. Surviving the crash: transitioning from effector to memory CD8+ T cell.
    Semin Immunol. 2009 Apr;21(2):92-8 PMID: 19269192
  17. Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche.
    J Immunol. 2010 Nov 1;185(9):4988-92 PMID: 20935204
  18. Interaction of NF-kappaB and NFAT with the interferon-gamma promoter.
    J Biol Chem. 1997 Nov 28;272(48):30412-20 PMID: 9374532
  19. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
    Science. 2009 Aug 21;325(5943):1006-10 PMID: 19608860
  20. CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-gamma locus.
    Immunity. 2009 Oct 16;31(4):551-64 PMID: 19818655
  21. IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508.
    J Exp Med. 2005 Nov 7;202(9):1289-300 PMID: 16275766
  22. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells.
    Immunity. 2010 Jan 29;32(1):79-90 PMID: 20096607
  23. NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression.
    Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2016-21 PMID: 15684054
  24. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.
    Immunity. 2009 Sep 18;31(3):457-68 PMID: 19631565
  25. Molecular mechanisms by which T-bet regulates T-helper cell commitment.
    Immunol Rev. 2010 Nov;238(1):233-46 PMID: 20969596
  26. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.
    Cell. 1997 May 16;89(4):587-96 PMID: 9160750
  27. Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.
    Immunity. 2009 Oct 16;31(4):539-50 PMID: 19833085
  28. T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes.
    Nat Immunol. 2002 Jul;3(7):643-51 PMID: 12055628
  29. Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation.
    Nat Immunol. 2010 Feb;11(2):114-20 PMID: 20084069
  30. Plasticity of CD4+ T cell lineage differentiation.
    Immunity. 2009 May;30(5):646-55 PMID: 19464987
  31. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.
    Science. 2002 Jan 11;295(5553):336-8 PMID: 11786643
  32. Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.
    Immunity. 2010 Jun 25;32(6):840-51 PMID: 20620946
  33. 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
  34. Encoding stability versus flexibility: lessons learned from examining epigenetics in T helper cell differentiation.
    Curr Top Microbiol Immunol. 2012;356:145-64 PMID: 21748629
  35. A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy.
    J Exp Med. 2008 Dec 22;205(13):3133-44 PMID: 19047438
  36. A novel transcription factor, T-bet, directs Th1 lineage commitment.
    Cell. 2000 Mar 17;100(6):655-69 PMID: 10761931
  37. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells.
    Science. 2002 Jan 11;295(5553):338-42 PMID: 11786644
  38. POZ for effect--POZ-ZF transcription factors in cancer and development.
    Trends Cell Biol. 2006 Nov;16(11):578-87 PMID: 16996269
  39. Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection.
    Nat Immunol. 2011 May 29;12(7):663-71 PMID: 21623380
  40. Differentiation of effector CD4 T cell populations (*).
    Annu Rev Immunol. 2010;28:445-89 PMID: 20192806
  41. Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells.
    Nat Immunol. 2002 Jun;3(6):558-63 PMID: 12021781
  42. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
    Cell. 2006 Sep 22;126(6):1121-33 PMID: 16990136
Article Info
Journal
Trends in immunology
Abbr.
Trends Immunol
ISSN
1471-4981
DOI
10.1016/j.it.2011.10.005
Published
2012-02-00
Epub
2011-00-29
Pages
78-83
Language
English
Region
England
NLM ID
100966032
PMCID
PMC3273642
Subset
IM
Grants
NIAID NIH HHS · AI07272 · United States
NIAID NIH HHS · R01 AI071272 · United States
NIAID NIH HHS · R01 AI061061-08 · United States
NIAID NIH HHS · T32 AI007272 · United States
NIAID NIH HHS · R01 AI061061 · United States
NIAID NIH HHS · R01 AI071272-10 · United States
NIAID NIH HHS · R56 AI061061 · United States
NIAID NIH HHS · AI061061 · United States
External Links
PubMed source DOI: 10.1016/j.it.2011.10.005 PMC Full Text View journal details
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