Home LiteratureArticle Details
PMID: 24113868 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

T-bet: a bridge between innate and adaptive immunity.

Nature reviews. Immunology ·Vol. 13 ·No. 11 ·2013-11-00 ·Pages 777-89

Lazarevic V, Glimcher LH, Lord GM

Abstract

Originally described over a decade ago as a T cell transcription factor regulating T helper 1 cell lineage commitment, T-bet is now recognized as having an important role in many cells of the adaptive and innate immune system. T-bet has a fundamental role in coordinating type 1 immune responses by controlling a network of genetic programmes that regulate the development of certain immune cells and the effector functions of others. Many of these transcriptional networks are conserved across innate and adaptive immune cells and these shared mechanisms highlight the biological functions that are regulated by T-bet.

MeSH Terms
Adaptive Immunity Animals B-Lymphocytes/immunology Humans Immunity, Innate Immunologic Memory T-Box Domain Proteins/physiology T-Lymphocyte Subsets/cytology,immunology,metabolism
Chemicals
T-Box Domain Proteins T-box transcription factor TBX21
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lazarevic Vanja
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glimcher Laurie H
Lord Graham M
References (107)
107 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. Fate mapping of IL-17-producing T cells in inflammatory responses.
    Nat Immunol. 2011 Mar;12(3):255-63 PMID: 21278737
  3. 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
  4. Increased susceptibility of mice lacking T-bet to infection with Mycobacterium tuberculosis correlates with increased IL-10 and decreased IFN-gamma production.
    J Immunol. 2005 Oct 1;175(7):4593-602 PMID: 16177104
  5. Induction and molecular signature of pathogenic TH17 cells.
    Nat Immunol. 2012 Oct;13(10):991-9 PMID: 22961052
  6. Evolutionarily conserved sequence elements that positively regulate IFN-gamma expression in T cells.
    Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12622-7 PMID: 15304658
  7. T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype.
    Blood. 2006 Sep 1;108(5):1595-601 PMID: 16670261
  8. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.
    Immunity. 2010 Nov 24;33(5):736-51 PMID: 21093318
  9. Control of effector CD8+ T cell function by the transcription factor Eomesodermin.
    Science. 2003 Nov 7;302(5647):1041-3 PMID: 14605368
  10. A validated regulatory network for Th17 cell specification.
    Cell. 2012 Oct 12;151(2):289-303 PMID: 23021777
  11. 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
  12. Induction of IgG2a class switching in B cells by IL-27.
    J Immunol. 2004 Aug 15;173(4):2479-85 PMID: 15294962
  13. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
    Nat Immunol. 2009 Jan;10(1):29-37 PMID: 19043418
  14. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues.
    Nat Immunol. 2013 Mar;14(3):221-9 PMID: 23334791
  15. Redefining chronic viral infection.
    Cell. 2009 Jul 10;138(1):30-50 PMID: 19596234
  16. CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines.
    Blood. 2012 Nov 29;120(23):4552-9 PMID: 23065152
  17. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.
    Immunity. 2010 Jan 29;32(1):116-28 PMID: 20079668
  18. MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells.
    Immunity. 2011 Aug 26;35(2):169-81 PMID: 21820330
  19. A distal conserved sequence element controls Ifng gene expression by T cells and NK cells.
    Immunity. 2006 Nov;25(5):717-29 PMID: 17070076
  20. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells.
    J Clin Invest. 2006 Feb;116(2):414-21 PMID: 16410834
  21. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs.
    J Exp Med. 2009 Jan 16;206(1):51-9 PMID: 19139168
  22. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.
    Cell. 2007 Oct 5;131(1):33-45 PMID: 17923086
  23. Innate lymphoid cells--a proposal for uniform nomenclature.
    Nat Rev Immunol. 2013 Feb;13(2):145-9 PMID: 23348417
  24. T-bet regulates IgG class switching and pathogenic autoantibody production.
    Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5545-50 PMID: 11960012
  25. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells.
    Immunity. 2011 Oct 28;35(4):622-32 PMID: 22018472
  26. Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.
    J Immunol. 2011 Oct 15;187(8):4068-76 PMID: 21930973
  27. Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells.
    Immunity. 2011 Oct 28;35(4):583-95 PMID: 22018468
  28. Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli.
    Immunity. 2010 Jul 23;33(1):35-47 PMID: 20643337
  29. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.
    Immunity. 2010 May 28;32(5):616-27 PMID: 20471290
  30. Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division.
    Immunity. 2011 Apr 22;34(4):492-504 PMID: 21497118
  31. Late developmental plasticity in the T helper 17 lineage.
    Immunity. 2009 Jan 16;30(1):92-107 PMID: 19119024
  32. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis.
    Cell Host Microbe. 2010 Sep 16;8(3):292-300 PMID: 20833380
  33. Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation.
    J Immunol. 2006 Dec 1;177(11):7515-9 PMID: 17114419
  34. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.
    Immunity. 2007 Aug;27(2):281-95 PMID: 17723218
  35. The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes.
    Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17876-81 PMID: 19805038
  36. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.
    Nat Immunol. 2005 Dec;6(12):1236-44 PMID: 16273099
  37. miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis.
    J Immunol. 2012 Aug 15;189(4):1567-76 PMID: 22772450
  38. Antigen-driven effector CD8 T cell function regulated by T-bet.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15818-23 PMID: 14673093
  39. The Ets-1 transcription factor is required for Stat1-mediated T-bet expression and IgG2a class switching in mouse B cells.
    Blood. 2012 May 3;119(18):4174-81 PMID: 22438254
  40. Early Th1 cell differentiation is marked by a Tfh cell-like transition.
    Immunity. 2011 Dec 23;35(6):919-31 PMID: 22195747
  41. 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
  42. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection.
    Science. 2001 Jun 8;292(5523):1907-10 PMID: 11397944
  43. 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
  44. Dual nature of the adaptive immune system in lampreys.
    Nature. 2009 Jun 11;459(7248):796-801 PMID: 19474790
  45. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation.
    Immunity. 2012 Mar 23;36(3):374-87 PMID: 22425248
  46. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12.
    Immunity. 2009 May;30(5):673-83 PMID: 19409816
  47. Differential expression of Ly6C and T-bet distinguish effector and memory Th1 CD4(+) cell properties during viral infection.
    Immunity. 2011 Oct 28;35(4):633-46 PMID: 22018471
  48. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells.
    Immunity. 2009 Jan 16;30(1):155-67 PMID: 19144320
  49. Origin and evolution of the adaptive immune system: genetic events and selective pressures.
    Nat Rev Genet. 2010 Jan;11(1):47-59 PMID: 19997068
  50. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells.
    Cancer Cell. 2009 Sep 8;16(3):208-19 PMID: 19732721
  51. Lysine 313 of T-box is crucial for modulation of protein stability, DNA binding, and threonine phosphorylation of T-bet.
    J Immunol. 2013 Jun 1;190(11):5764-70 PMID: 23616576
  52. The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells.
    Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13248-53 PMID: 16135562
  53. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile.
    Nat Immunol. 2012 Mar 11;13(4):405-11 PMID: 22406686
  54. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction.
    Nat Immunol. 2002 Jul;3(7):652-8 PMID: 12055627
  55. The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology.
    Immunity. 2012 Sep 21;37(3):511-23 PMID: 22981537
  56. Evolution of developmental functions by the Eomesodermin, T-brain-1, Tbx21 subfamily of T-box genes: insights from amphioxus.
    J Exp Zool. 2002 Aug 15;294(2):112-21 PMID: 12210112
  57. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation.
    Nat Immunol. 2009 Jun;10(6):595-602 PMID: 19412181
  58. Master transcription factors and mediator establish super-enhancers at key cell identity genes.
    Cell. 2013 Apr 11;153(2):307-19 PMID: 23582322
  59. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin.
    Immunity. 2010 Jan 29;32(1):67-78 PMID: 20060330
  60. The development of airway hyperreactivity in T-bet-deficient mice requires CD1d-restricted NKT cells.
    J Immunol. 2009 Mar 1;182(5):3252-61 PMID: 19234223
  61. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells.
    Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7749-54 PMID: 12802010
  62. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells.
    J Exp Med. 2007 Sep 3;204(9):2015-21 PMID: 17698591
  63. T-Bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-gamma by gammadelta T cells.
    J Immunol. 2002 Feb 15;168(4):1566-71 PMID: 11823483
  64. Innate lymphoid cells: emerging insights in development, lineage relationships, and function.
    Annu Rev Immunol. 2012;30:647-75 PMID: 22224763
  65. 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
  66. Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin.
    Science. 2008 Jul 18;321(5887):408-11 PMID: 18635804
  67. T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2.
    Immunity. 2012 Sep 21;37(3):501-10 PMID: 22960221
  68. Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination.
    Immunity. 2008 Nov 14;29(5):679-90 PMID: 18993086
  69. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells.
    Immunity. 2012 Oct 19;37(4):674-84 PMID: 23063332
  70. Molecular mechanisms by which T-bet regulates T-helper cell commitment.
    Immunol Rev. 2010 Nov;238(1):233-46 PMID: 20969596
  71. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages.
    Nat Immunol. 2011 Jun;12(6):551-9 PMID: 21516110
  72. 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
  73. Stat1-dependent synergistic activation of T-bet for IgG2a production during early stage of B cell activation.
    J Immunol. 2005 Dec 1;175(11):7419-24 PMID: 16301649
  74. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types.
    Immunity. 2011 Aug 26;35(2):299-311 PMID: 21867929
  75. T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells.
    Immunity. 2004 Apr;20(4):477-94 PMID: 15084276
  76. 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
  77. STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms.
    J Immunol. 2010 Dec 1;185(11):6461-71 PMID: 20974984
  78. 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
  79. T-bet is essential for encephalitogenicity of both Th1 and Th17 cells.
    J Exp Med. 2009 Jul 6;206(7):1549-64 PMID: 19546248
  80. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma.
    Immunity. 2010 Apr 23;32(4):507-17 PMID: 20399120
  81. Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection.
    Immunity. 2013 Apr 18;38(4):805-17 PMID: 23583644
  82. Transcriptional regulation of the mucosal immune system mediated by T-bet.
    Mucosal Immunol. 2010 Nov;3(6):567-77 PMID: 20844482
  83. Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue.
    J Exp Med. 2007 Feb 19;204(2):431-9 PMID: 17296784
  84. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15137-42 PMID: 11752460
  85. Epigenetic and transcriptional programs lead to default IFN-gamma production by gammadelta T cells.
    J Immunol. 2007 Mar 1;178(5):2730-6 PMID: 17312115
  86. 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
  87. STATs shape the active enhancer landscape of T cell populations.
    Cell. 2012 Nov 21;151(5):981-93 PMID: 23178119
  88. A T-bet gradient controls the fate and function of CCR6-RORγt+ innate lymphoid cells.
    Nature. 2013 Feb 14;494(7436):261-5 PMID: 23334414
  89. T-bet is required for optimal proinflammatory CD4+ T-cell trafficking.
    Blood. 2005 Nov 15;106(10):3432-9 PMID: 16014561
  90. Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection.
    Science. 2012 Nov 30;338(6111):1220-5 PMID: 23197535
  91. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells.
    Immunity. 2013 Apr 18;38(4):769-81 PMID: 23453631
  92. A novel transcription factor, T-bet, directs Th1 lineage commitment.
    Cell. 2000 Mar 17;100(6):655-69 PMID: 10761931
  93. 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
  94. Divergent transcriptional programming of class-specific B cell memory by T-bet and RORα.
    Nat Immunol. 2012 May 06;13(6):604-11 PMID: 22561605
  95. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses.
    Immunity. 2012 Oct 19;37(4):660-73 PMID: 23041064
  96. T-bet plays a key role in NK-mediated control of melanoma metastatic disease.
    J Immunol. 2008 Jun 15;180(12):8004-10 PMID: 18523263
  97. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.
    Immunity. 2012 Jan 27;36(1):55-67 PMID: 22261438
  98. 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
  99. T-bet concomitantly controls migration, survival, and effector functions during the development of Valpha14i NKT cells.
    Blood. 2006 Apr 1;107(7):2797-805 PMID: 16357323
  100. 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
  101. 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
  102. Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection.
    J Immunol. 2005 Oct 1;175(7):4603-10 PMID: 16177105
  103. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements.
    Nat Commun. 2012;3:1268 PMID: 23232398
  104. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
    Nature. 2010 Oct 21;467(7318):967-71 PMID: 20962846
  105. Distinct requirements for T-bet in gut innate lymphoid cells.
    J Exp Med. 2012 Dec 17;209(13):2331-8 PMID: 23209316
  106. Inflammatory bowel disease--live transmission.
    N Engl J Med. 2008 Jan 31;358(5):528-30 PMID: 18234759
  107. T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells.
    Nat Immunol. 2002 Jun;3(6):549-57 PMID: 12006974
Article Info
Journal
Nature reviews. Immunology
Abbr.
Nat Rev Immunol
ISSN
1474-1741
DOI
10.1038/nri3536
Published
2013-11-00
Epub
2013-00-11
Pages
777-89
Language
English
Region
England
NLM ID
101124169
PMCID
PMC6290922
Subset
IM
Grants
Wellcome Trust · WT088747MA · United Kingdom
Intramural NIH HHS · ZIA BC011431-02 · United States
NCI NIH HHS · R01 CA112663 · United States
Medical Research Council · G0802068 · United Kingdom
Medical Research Council · MR/J006742/1 · United Kingdom
NCI NIH HHS · CA112663 · United States
Wellcome Trust · United Kingdom
PHS HHS · P01NSO38037 · United States
British Heart Foundation · PG/12/36/29444 · United Kingdom
Medical Research Council · G1000758 · United Kingdom
External Links
PubMed source DOI: 10.1038/nri3536 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2