Tbx21

Summary

Gene Symbol: Tbx21
Description: T-box 21
Alias: TBT1, Tbet, Tblym, T-box transcription factor TBX21, T-box protein 21, T-cell-specific T-box transcription factor T-bet, transcription factor TBLYM
Species: mouse
Products:     Tbx21

Top Publications

  1. Lovett Racke A, Rocchini A, Choy J, Northrop S, Hussain R, Ratts R, et al. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity. 2004;21:719-31 pubmed
    ..Since T-bet regulates IFNgamma production in CD4(+) T cells, but to a lesser extent in most other IFNgamma-producing cells, T-bet may be a target for therapeutics for Th1-mediated diseases. ..
  2. Usui T, Preiss J, Kanno Y, Yao Z, Bream J, O Shea J, et al. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med. 2006;203:755-66 pubmed
    ..Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene. ..
  3. Mathur A, Chang H, Zisoulis D, Kapur R, Belladonna M, Kansas G, et al. T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood. 2006;108:1595-601 pubmed
    ..Th1 or Th1beta Tbx21-/- cultures secrete higher than WT levels of IL-17 in response to T-cell receptor (TCR) or IL-23 + IL-18 ..
  4. Lewis M, Miller S, Miazgowicz M, Beima K, Weinmann A. 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;27:8510-21 pubmed
    ..The requirement for two separable functional activities may ultimately contribute to the stringent role for T-box proteins in establishing specific developmental gene expression pathways. ..
  5. Koch M, Tucker Heard G, Perdue N, Killebrew J, Urdahl K, Campbell D. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol. 2009;10:595-602 pubmed publisher
  6. Townsend M, Weinmann A, Matsuda J, Salomon R, Farnham P, Biron C, et al. T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity. 2004;20:477-94 pubmed
    ..Our results identify T-bet as a key factor in the terminal maturation and peripheral homeostasis of NK and Valpha14i NKT cells. ..
  7. Wang Y, Godec J, Ben Aissa K, Cui K, Zhao K, Pucsek A, et al. The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells. Immunity. 2014;40:355-66 pubmed publisher
    ..Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-γ-producing Th17 cells. ..
  8. Durrant D, Gaffen S, Riesenfeld E, Irvin C, Metzger D. Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17. J Immunol. 2009;183:5293-300 pubmed publisher
    ..These findings indicate that IL-17 is a key mediator of airway inflammation in the absence of T-bet. The results of this study suggest a possible target for therapeutic intervention of human asthma. ..
  9. Lee Y, Turner H, Maynard C, Oliver J, Chen D, Elson C, et al. Late developmental plasticity in the T helper 17 lineage. Immunity. 2009;30:92-107 pubmed publisher
    ..These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense. ..

More Information

Publications85

  1. Garrett W, Lord G, Punit S, Lugo Villarino G, Mazmanian S, Ito S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131:33-45 pubmed
    ..These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD. ..
  2. Park J, Min H, Sohn J, Kim J, Hong J, Sigrist K, et al. Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma. J Allergy Clin Immunol. 2009;123:479-85 pubmed publisher
    ..Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma. ..
  3. Bettelli E, Sullivan B, Szabo S, Sobel R, Glimcher L, Kuchroo V. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med. 2004;200:79-87 pubmed
    ..Although the two transcription factors, STAT1 and T-bet, both induce IFN-gamma gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses. ..
  4. Oestreich K, Huang A, Weinmann A. The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns. J Exp Med. 2011;208:1001-13 pubmed publisher
  5. Kanhere A, Hertweck A, Bhatia U, Gökmen M, Perucha E, Jackson I, et al. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements. Nat Commun. 2012;3:1268 pubmed publisher
    ..Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression...
  6. Intlekofer A, Banerjee A, Takemoto N, Gordon S, Dejong C, Shin H, et al. Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science. 2008;321:408-11 pubmed publisher
    ..T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction. ..
  7. Jenner R, Townsend M, Jackson I, Sun K, Bouwman R, Young R, et al. 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;106:17876-81 pubmed publisher
  8. Duhen R, Glatigny S, Arbelaez C, Blair T, Oukka M, Bettelli E. Cutting edge: the pathogenicity of IFN-γ-producing Th17 cells is independent of T-bet. J Immunol. 2013;190:4478-82 pubmed publisher
    ..Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-γ expression in Th1 and Th17 cells. ..
  9. Szabo S, Sullivan B, Stemmann C, Satoskar A, Sleckman B, Glimcher L. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science. 2002;295:338-42 pubmed
    ..This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage. ..
  10. Gordon S, Chaix J, Rupp L, Wu J, Madera S, Sun J, et al. The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. Immunity. 2012;36:55-67 pubmed publisher
    ..These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis. ..
  11. Shinohara M, Jansson M, Hwang E, Werneck M, Glimcher L, Cantor H. T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc Natl Acad Sci U S A. 2005;102:17101-6 pubmed
    ..Taken together, these findings begin to delineate the genetic basis of Opn expression in T cells and further clarify the role of Opn in Th and Tc1 development. ..
  12. Jenne C, Enders A, Rivera R, Watson S, Bankovich A, Pereira J, et al. T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. J Exp Med. 2009;206:2469-81 pubmed publisher
    ..This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein...
  13. Kondo Y, Iizuka M, Wakamatsu E, Yao Z, Tahara M, Tsuboi H, et al. Overexpression of T-bet gene regulates murine autoimmune arthritis. Arthritis Rheum. 2012;64:162-72 pubmed publisher
    ..Unlike the B6 mice, the T-bet-Tg mice did not develop CIA. T-bet-Tg mice showed overexpression of Tbx21 and down-regulation of Rorc in CII-reactive T cells...
  14. Qui H, Hagymasi A, Bandyopadhyay S, St Rose M, Ramanarasimhaiah R, Menoret A, et al. CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol. 2011;187:3555-64 pubmed publisher
    ..This mechanism might be therapeutically useful because CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model. ..
  15. Siebler J, Wirtz S, Frenzel C, Schuchmann M, Lohse A, Galle P, et al. Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis. J Immunol. 2008;180:30-3 pubmed
    ..Taken together, these data demonstrate a key pathogenic role of IL-27 in T cell-mediated liver injury. Furthermore, in vivo blockade of IL-27 emerges as a novel potential therapy for T cell-mediated hepatitis. ..
  16. Oldenhove G, Bouladoux N, Wohlfert E, Hall J, Chou D, Dos Santos L, et al. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity. 2009;31:772-86 pubmed publisher
    ..These data reveal a mechanism for Th1 cell pathogenicity that extends beyond their proinflammatory program to limit Treg cell survival. ..
  17. Lazarevic V, Chen X, Shim J, Hwang E, Jang E, Bolm A, et al. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR?t. Nat Immunol. 2011;12:96-104 pubmed publisher
    ..Our data reinforce the idea of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell. ..
  18. Neurath M, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, et al. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J Exp Med. 2002;195:1129-43 pubmed
    ..Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes. ..
  19. Powell N, Walker A, Stolarczyk E, Canavan J, Gökmen M, Marks E, et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity. 2012;37:674-84 pubmed publisher
    ..that interleukin-17A (IL-17A)-producing IL-7R?(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice...
  20. Klose C, Kiss E, Schwierzeck V, Ebert K, Hoyler T, d Hargues Y, et al. A T-bet gradient controls the fate and function of CCR6-ROR?t+ innate lymphoid cells. Nature. 2013;494:261-5 pubmed publisher
  21. Pearce E, Mullen A, Martins G, Krawczyk C, Hutchins A, Zediak V, et al. Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science. 2003;302:1041-3 pubmed
    ..We suggest that Eomesodermin is likely to complement the actions of T-bet and act as a key regulatory gene in the development of cell-mediated immunity. ..
  22. Furuta S, Kagami S, Tamachi T, Ikeda K, Fujiwara M, Suto A, et al. Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation. J Immunol. 2008;180:6656-62 pubmed
    ..These results indicate that STAT4 not only plays an indispensable role in T-bet-independent Th1 differentiation but also is involved in the maintenance of Th17 cells and the enhancement of allergic airway inflammation. ..
  23. Intlekofer A, Takemoto N, Kao C, Banerjee A, Schambach F, Northrop J, et al. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. J Exp Med. 2007;204:2015-21 pubmed
    ..T-bet, thus, appears to function as a molecular switch between central- and effector-memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells. ..
  24. Mehta D, Wurster A, Weinmann A, Grusby M. NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression. Proc Natl Acad Sci U S A. 2005;102:2016-21 pubmed
    ..These data suggest that there are multiple mechanisms by which Th-cell-subset-specific cytokine genes are regulated. ..
  25. Miller S, Mohn S, Weinmann A. Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Mol Cell. 2010;40:594-605 pubmed publisher
    ..This function for H3K27 demethylase proteins may explain their presence in differentiated cells where the epigenetic profile is already established. ..
  26. Phoon R, Kitching A, Odobasic D, Jones L, Semple T, Holdsworth S. T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 2008;19:477-85 pubmed publisher
    ..We conclude that T-bet directs Th1 responses that induce renal injury in experimental crescentic glomerulonephritis...
  27. Hwang E, Szabo S, Schwartzberg P, Glimcher L. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science. 2005;307:430-3 pubmed
    ..These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell. ..
  28. Taqueti V, Grabie N, Colvin R, Pang H, Jarolim P, Luster A, et al. T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity. J Immunol. 2006;177:5890-901 pubmed
    ..These findings highlight the potential therapeutic benefit of targeting T-bet-regulated gene expression and CXCR3-dependent migration in immune-mediated heart disease. ..
  29. Liao W, Lin J, Wang L, Li P, Leonard W. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat Immunol. 2011;12:551-9 pubmed publisher
    ..Thus, IL-2 influences helper T cell differentiation by modulating the expression of cytokine receptors to help specify and maintain differentiated states. ..
  30. Ghoreschi K, Laurence A, Yang X, Tato C, McGeachy M, Konkel J, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature. 2010;467:967-71 pubmed publisher
    ..These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications. ..
  31. Stumhofer J, Laurence A, Wilson E, Huang E, Tato C, Johnson L, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006;7:937-45 pubmed
    ..Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells. ..
  32. Collins P, Chang S, Henderson M, Soutto M, Davis G, McLoed A, et al. Distal regions of the human IFNG locus direct cell type-specific expression. J Immunol. 2010;185:1492-501 pubmed publisher
    ..These results support a model whereby IFNG uses cis-regulatory elements with cell type-restricted function. ..
  33. Bakshi C, Malik M, Carrico P, Sellati T. T-bet deficiency facilitates airway colonization by Mycoplasma pulmonis in a murine model of asthma. J Immunol. 2006;177:1786-95 pubmed
    ..For its part, airways exhibiting an asthmatic phenotype provide a fertile environment that promotes colonization by Mycoplasma spp. and one which is ill-equipped to kill and clear respiratory pathogens...
  34. Hultgren O, Verdrengh M, Tarkowski A. T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis. Microbes Infect. 2004;6:529-35 pubmed
    ..aureus infection, protecting against bacterial accumulation, cachexia and septic death. Furthermore T-bet downregulates joint inflammation in the early phase of disease. ..
  35. Sciumè G, Hirahara K, Takahashi H, Laurence A, Villarino A, Singleton K, et al. Distinct requirements for T-bet in gut innate lymphoid cells. J Exp Med. 2012;209:2331-8 pubmed publisher
    ..Herein, we show that T-bet (encoded by Tbx21) was highly expressed in NKp46+ ILC22, a feature shared by all NKp46+ cells present in the intestine but not by ..
  36. Nath N, Prasad R, Giri S, Singh A, Singh I. T-bet is essential for the progression of experimental autoimmune encephalomyelitis. Immunology. 2006;118:384-91 pubmed
    ..These data indicate that T-bet genes play a critical role in maintaining the encephalitogenic nature of CD4+ T cells in autoimmune responses during EAE disease progression. ..
  37. Oestreich K, Mohn S, Weinmann A. 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;13:405-11 pubmed publisher
    ..Thus, IL-2-signaling regulates the Bcl-6-Blimp-1 axis in T(H)1 cells to maintain flexibility with a T(FH) cell-like gene profile. ..
  38. Rao R, Li Q, Odunsi K, Shrikant P. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity. 2010;32:67-78 pubmed publisher
    ..Targeting mTOR activity offers new opportunities to regulate CD8+ T cell-mediated immunity. ..
  39. Robbins S, Tessmer M, Van Kaer L, Brossay L. Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral NK cell maturation. Eur J Immunol. 2005;35:757-65 pubmed
  40. Finotto S, Neurath M, Glickman J, Qin S, Lehr H, Green F, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science. 2002;295:336-8 pubmed
    ..Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma. ..
  41. Miller S, Huang A, Miazgowicz M, Brassil M, Weinmann A. 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;22:2980-93 pubmed publisher
    ..These novel mechanisms for T-box-mediated epigenetic regulation are essential, because point mutations that disrupt these interactions are found in a diverse array of human developmental genetic diseases. ..
  42. Das J, Ren G, Zhang L, Roberts A, Zhao X, Bothwell A, et al. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med. 2009;206:2407-16 pubmed publisher
    ..Collectively, these data provide evidence that TGF-beta is not directly required for the molecular orchestration of Th17 cell differentiation. ..
  43. Mullen A, Hutchins A, High F, Lee H, Sykes K, Chodosh L, et al. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction. Nat Immunol. 2002;3:652-8 pubmed
    ..These findings suggest that heritable states of gene expression might be maintained by continued expression of the inducing factor or by a mechanism that confers a stable imprint of the induced state. ..
  44. Garrett W, Punit S, Gallini C, Michaud M, Zhang D, Sigrist K, et al. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell. 2009;16:208-19 pubmed publisher
    ..TRUC colitis-associated colorectal cancer resembles the human disease and provides ample opportunity to probe how inflammation drives colorectal cancer development and to test preventative and therapeutic strategies preclinically. ..
  45. Cruz Guilloty F, Pipkin M, Djuretic I, Levanon D, Lotem J, Lichtenheld M, et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med. 2009;206:51-9 pubmed publisher
    ..Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs. ..
  46. Lugo Villarino G, Maldonado Lopez R, Possemato R, Penaranda C, Glimcher L. 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;100:7749-54 pubmed
    ..The rapid up-regulation of T-bet by IFN-gamma in DCs coupled with a function for DC-derived IFN-gamma in T cell activation may constitute a positive feedback loop to maximize type 1 immunity. ..
  47. Kiwamoto T, Ishii Y, Morishima Y, Yoh K, Maeda A, Ishizaki K, et al. Transcription factors T-bet and GATA-3 regulate development of airway remodeling. Am J Respir Crit Care Med. 2006;174:142-51 pubmed
    ..Overall, the results indicate that development of airway remodeling is regulated by the lung Th1/Th2 bias induced by GATA-3 and T-bet. ..
  48. Ishizaki K, Yamada A, Yoh K, Nakano T, Shimohata H, Maeda A, et al. Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression transgenic mice that develop contact dermatitis. J Immunol. 2007;178:605-12 pubmed
    ..These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis. ..
  49. Kao C, Oestreich K, Paley M, Crawford A, Angelosanto J, Ali M, et al. 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;12:663-71 pubmed publisher
    ..Persistent antigenic stimulation caused downregulation of T-bet, which resulted in more severe exhaustion of CD8(+) T cells. Our observations suggest therapeutic opportunities involving higher T-bet expression during chronic infection...
  50. Finotto S, Hausding M, Doganci A, Maxeiner J, Lehr H, Luft C, et al. Asthmatic changes in mice lacking T-bet are mediated by IL-13. Int Immunol. 2005;17:993-1007 pubmed
    ..These data highlight a T-bet-directed function for IL-13 in controlling lung remodeling that is both dependent on and independent of its interaction with TGF-beta in the asthmatic airway. ..
  51. Sullivan B, Juedes A, Szabo S, von Herrath M, Glimcher L. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc Natl Acad Sci U S A. 2003;100:15818-23 pubmed
    ..Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic choriomeningitis virus. T-bet is a key player in the generation of type 1 immunity, in both Th and T cytotoxic cells...
  52. El Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011;12:568-75 pubmed publisher
    ..Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies T(H)17 cells as a crucial source of GM-CSF in autoimmune inflammation. ..
  53. Szabo S, Kim S, Costa G, Zhang X, Fathman C, Glimcher L. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655-69 pubmed
    ..Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs. ..
  54. Yang Y, Ochando J, Bromberg J, Ding Y. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood. 2007;110:2494-500 pubmed
    ..Together, we provide a novel mechanism for T-bet regulation, and suggest that IL-12/Stat4/T-bet play an important role in CD8 effector responses. ..
  55. Juedes A, Rodrigo E, Togher L, Glimcher L, Von Herrath M. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. J Exp Med. 2004;199:1153-62 pubmed
    ..This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders. ..
  56. Xu J, Yang Y, Qiu G, Lal G, Wu Z, Levy D, et al. c-Maf regulates IL-10 expression during Th17 polarization. J Immunol. 2009;182:6226-36 pubmed publisher
    ..Taken together, these data reveal a novel role for c-Maf in regulating T effector development, and they suggest that TGFbeta may antagonize Th17 immunity by IL-10 production through c-Maf induction. ..
  57. Veiga P, Gallini C, Beal C, Michaud M, Delaney M, DuBois A, et al. Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes. Proc Natl Acad Sci U S A. 2010;107:18132-7 pubmed publisher
    ..lactis-containing fermented milk product, and therefore this model provides a framework for evaluating and optimizing probiotic-based functional foods...
  58. Underhill G, Zisoulis D, Kolli K, Ellies L, Marth J, Kansas G. A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells. Blood. 2005;106:3867-73 pubmed
  59. Buono C, Binder C, Stavrakis G, Witztum J, Glimcher L, Lichtman A. T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses. Proc Natl Acad Sci U S A. 2005;102:1596-601 pubmed
    ..These findings establish that T cell subset differentiation influences both T cell and antibody responses that modulate atherosclerosis, and validate the therapeutic goal of skewing T responses to atherosclerosis-associated antigens. ..
  60. Yeh W, McWilliams I, Harrington L. Autoreactive Tbet-positive CD4 T cells develop independent of classic Th1 cytokine signaling during experimental autoimmune encephalomyelitis. J Immunol. 2011;187:4998-5006 pubmed publisher
    ..principal Th1 cytokine IFN-? does not appear necessary for disease, but the key Th1-associated transcription factor Tbet has been reported to be essential for disease development...
  61. Balasubramani A, Shibata Y, Crawford G, Baldwin A, Hatton R, Weaver C. Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity. 2010;33:35-47 pubmed publisher
    ..These results support a model of Ifng regulation in which distal cis-regulatory elements differentially recruit key transcription factors in a modular fashion to initiate gene transcription induced by distinct activation signals. ..
  62. Usui T, Nishikomori R, Kitani A, Strober W. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity. 2003;18:415-28 pubmed
    ..These findings reassert that Stat4 signaling is a central element of Th1/Th2 development. ..
  63. Zhu J, Jankovic D, Oler A, Wei G, Sharma S, Hu G, et al. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity. 2012;37:660-73 pubmed publisher
    ..Our study revealed redundancy and synergy among several Th1 cell-inducing pathways in regulating the expression of T-bet and IFN-γ, and a critical role of T-bet in suppressing an endogenous Th2 cell-associated program. ..
  64. Hegazy A, Peine M, Helmstetter C, Panse I, Fröhlich A, Bergthaler A, et al. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity. 2010;32:116-28 pubmed publisher
    ..Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells. ..
  65. Nakayamada S, Kanno Y, Takahashi H, Jankovic D, Lu K, Johnson T, et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity. 2011;35:919-31 pubmed publisher
    ..Our data argue that Tfh and Th1 cells share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh cell functionalities, promoting full Th1 cell differentiation. ..
  66. Guo S, Cobb D, Smeltz R. T-bet inhibits the in vivo differentiation of parasite-specific CD4+ Th17 cells in a T cell-intrinsic manner. J Immunol. 2009;182:6179-86 pubmed publisher
    ..Infection of Tbx21(-/-) mice led to normal, unimpaired development of Ag-specific CD4(+) T cells producing IFN-gamma...
  67. Esensten J, Lee M, Glimcher L, Bluestone J. T-bet-deficient NOD mice are protected from diabetes due to defects in both T cell and innate immune system function. J Immunol. 2009;183:75-82 pubmed publisher
    The transcription factor T-bet (Tbx21) is critical for Th1 polarization of CD4(+) T cells. Genetic deletion of Tbx21 can cause either exacerbation or attenuation of different autoimmune diseases in animal models...
  68. Matsui M, Moriya O, Yoshimoto T, Akatsuka T. T-bet is required for protection against vaccinia virus infection. J Virol. 2005;79:12798-806 pubmed
  69. Harrington L, Hatton R, Mangan P, Turner H, Murphy T, Murphy K, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123-32 pubmed
    ..These findings provide a basis for understanding how inhibition of IFN-gamma signaling enhances development of pathogenic T(H)-17 effector cells that can exacerbate autoimmunity. ..
  70. Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein J, Bulfone A. Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis. Mech Dev. 2002;116:157-60 pubmed
    ..expression pattern of a new member of the Tbr1 subfamily of T-box genes; this gene has been recently named T-bet/Tbx21 (Genomics 70 (2000) 41; Cell 17 (2000) 655; Science 292 (2001) 1907; Science 295 (2002) 338)...
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    The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-gamma production by DCs. Here we demonstrate an essential function for T-bet in DCs in controlling inflammatory arthritis...
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    ..Therefore, these key transcription factors link the long-term renewal of memory CD8(+) T cells to their characteristic effector potency. ..
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    ..Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development. ..
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    ..These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential. ..