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

Top Publications

  1. ncbi Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes
    Amy E Lovett-Racke
    Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 USA
    Immunity 21:719-31. 2004
  2. pmc T-bet is required for optimal proinflammatory CD4+ T-cell trafficking
    Graham M Lord
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Blood 106:3432-9. 2005
  3. pmc T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription
    Takashi Usui
    Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease NIAID, National Institutes of Health NIH, Bethesda, MD 20892, USA
    J Exp Med 203:755-66. 2006
  4. pmc T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype
    Anubhav N Mathur
    Department Microbiology and Immunology, Indiana University School of Medicine, 702 Barnhill Dr, RI 2600, Indianapolis, IN 46202, USA
    Blood 108:1595-601. 2006
  5. pmc 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
    Megan D Lewis
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Mol Cell Biol 27:8510-21. 2007
  6. ncbi A novel transcription factor, T-bet, directs Th1 lineage commitment
    S J Szabo
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Cell 100:655-69. 2000
  7. ncbi Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
    Laurie E Harrington
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Nat Immunol 6:1123-32. 2005
  8. pmc A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
    Heon Park
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 6:1133-41. 2005
  9. ncbi Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction
    Alan C Mullen
    Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Nat Immunol 3:652-8. 2002
  10. pmc The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes
    Richard G Jenner
    MRC UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London W1T 4JF, United Kingdom
    Proc Natl Acad Sci U S A 106:17876-81. 2009

Research Grants

Scientific Experts

Detail Information

Publications147 found, 100 shown here

  1. ncbi Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes
    Amy E Lovett-Racke
    Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 USA
    Immunity 21:719-31. 2004
    ..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. pmc T-bet is required for optimal proinflammatory CD4+ T-cell trafficking
    Graham M Lord
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Blood 106:3432-9. 2005
    ..T-bet is also required for the expression of the chemokine receptor CXCR3. Thus, T-bet controls Th1-cell migration to inflammatory sites, which has fundamental consequences for the control of immunologic disease...
  3. pmc T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription
    Takashi Usui
    Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease NIAID, National Institutes of Health NIH, Bethesda, MD 20892, USA
    J Exp Med 203:755-66. 2006
    ..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...
  4. pmc T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype
    Anubhav N Mathur
    Department Microbiology and Immunology, Indiana University School of Medicine, 702 Barnhill Dr, RI 2600, Indianapolis, IN 46202, USA
    Blood 108:1595-601. 2006
    ..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 ..
  5. pmc 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
    Megan D Lewis
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Mol Cell Biol 27:8510-21. 2007
    ..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...
  6. ncbi A novel transcription factor, T-bet, directs Th1 lineage commitment
    S J Szabo
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Cell 100:655-69. 2000
    ..Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs...
  7. ncbi Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
    Laurie E Harrington
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Nat Immunol 6:1123-32. 2005
    ..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...
  8. pmc A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
    Heon Park
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 6:1133-41. 2005
    ..Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation...
  9. ncbi Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction
    Alan C Mullen
    Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Nat Immunol 3:652-8. 2002
    ..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...
  10. pmc The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes
    Richard G Jenner
    MRC UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London W1T 4JF, United Kingdom
    Proc Natl Acad Sci U S A 106:17876-81. 2009
    ....
  11. pmc Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation
    Jyoti Das
    Department of Molecular Genetics, Microbiology, and Immunology, Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
    J Exp Med 206:2407-16. 2009
    ..Collectively, these data provide evidence that TGF-beta is not directly required for the molecular orchestration of Th17 cell differentiation...
  12. ncbi T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3
    Eun Sook Hwang
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Science 307:430-3. 2005
    ..These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell...
  13. pmc T-bet, a Th1 transcription factor regulates the expression of Tim-3
    Ana C Anderson
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Eur J Immunol 40:859-66. 2010
    ....
  14. pmc IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine
    Elodie Mohr
    Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Proc Natl Acad Sci U S A 107:17292-7. 2010
    ..Thus, T-bet dependence identifies distinct transcriptional pathways in B cells that regulate IFN-γ-induced switching to different IgG isotypes...
  15. ncbi T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells
    Michael J Townsend
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA
    Immunity 20:477-94. 2004
    ..Our results identify T-bet as a key factor in the terminal maturation and peripheral homeostasis of NK and Valpha14i NKT cells...
  16. pmc Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells
    Jingsong Wang
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    J Clin Invest 116:414-21. 2006
    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...
  17. pmc T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow
    Craig N Jenne
    Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 206:2469-81. 2009
    ..This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein...
  18. ncbi Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells
    Ivana M Djuretic
    Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Nat Immunol 8:145-53. 2007
    ..Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing...
  19. ncbi Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral NK cell maturation
    Scott H Robbins
    Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, USA
    Eur J Immunol 35:757-65. 2005
    ....
  20. pmc Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs
    Fernando Cruz-Guilloty
    Harvard Medical School and the Immune Disease Institute, Boston, MA 02115, USA
    J Exp Med 206:51-9. 2009
    ..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...
  21. pmc Antigen-driven effector CD8 T cell function regulated by T-bet
    Brandon M Sullivan
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:15818-23. 2003
    ..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...
  22. pmc Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation
    Min Shi
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunity 28:763-73. 2008
    ..These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation...
  23. doi T-bet inhibits the in vivo differentiation of parasite-specific CD4+ Th17 cells in a T cell-intrinsic manner
    Siqi Guo
    Department of Microbiology and Immunology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298, USA
    J Immunol 182:6179-86. 2009
    ..Infection of Tbx21(-/-) mice led to normal, unimpaired development of Ag-specific CD4(+) T cells producing IFN-gamma...
  24. pmc Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals
    Yu Yang
    Departments of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    Blood 110:2494-500. 2007
    ..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...
  25. pmc The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease
    M F Neurath
    Laboratory of Immunology, I Medical Clinic, University of Mainz, 55131 Mainz, Germany
    J Exp Med 195:1129-43. 2002
    ..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...
  26. pmc T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses
    Chiara Buono
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:1596-601. 2005
    ..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...
  27. ncbi Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression
    Maria Cecilia Rodriguez-Galan
    Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
    J Immunol 174:2796-804. 2005
    ....
  28. pmc T-bet-dependent expression of osteopontin contributes to T cell polarization
    Mari L Shinohara
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:17101-6. 2005
    ..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...
  29. pmc IFN-gamma-inducing transcription factor, T-bet is upregulated by estrogen in murine splenocytes: role of IL-27 but not IL-12
    Ebru Karpuzoglu
    Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA
    Mol Immunol 44:1808-14. 2007
    ..Given that T-bet is a potent inducer of IFN-gamma, these studies may lead to new lines of investigation in relation to many female-predominant autoimmune diseases and inflammatory disorders...
  30. pmc Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression
    Sara A Miller
    Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195, USA
    Genes Dev 22:2980-93. 2008
    ..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...
  31. ncbi Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet
    Susetta Finotto
    Critical Care and Pulmonary Division, Division of Gastroenterology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 295:336-8. 2002
    ..Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma...
  32. ncbi Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells
    Susanne J Szabo
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Science 295:338-42. 2002
    ..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...
  33. pmc T-bet regulates IgG class switching and pathogenic autoantibody production
    Stanford L Peng
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115 6017, USA
    Proc Natl Acad Sci U S A 99:5545-50. 2002
    ..These results identify T-bet as a selective transducer of IFN-gamma-mediated IgG2a class switching in B cells and emphasize the importance of this regulation in the pathogenesis of humorally mediated autoimmunity...
  34. ncbi T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells
    Maryam Afkarian
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 S Euclid Ave, St Louis, MO 63110, USA
    Nat Immunol 3:549-57. 2002
    ..Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In addition, T-bet mediates STAT1-dependent processes of T(H)1 development, including the induction of IL-12Rbeta2...
  35. ncbi Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis
    Andrea Faedo
    Stem Cell Research Institute SCRI, Istituto Scientifico HS Raffaele, Via Olgettina, 58 Milan, Italy
    Mech Dev 116:157-60. 2002
    ..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)...
  36. ncbi GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet
    Takashi Usui
    Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 18:415-28. 2003
    ..These findings reassert that Stat4 signaling is a central element of Th1/Th2 development...
  37. pmc T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells
    Geanncarlo Lugo-Villarino
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115 6017, USA
    Proc Natl Acad Sci U S A 100:7749-54. 2003
    ..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...
  38. ncbi Control of effector CD8+ T cell function by the transcription factor Eomesodermin
    Erika L Pearce
    Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 302:1041-3. 2003
    ..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...
  39. pmc T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes
    Amy E Juedes
    Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr, San Diego, CA 92121, USA
    J Exp Med 199:1153-62. 2004
    ..This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders...
  40. pmc Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis
    Estelle Bettelli
    Center for Neurologic Diseases, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Exp Med 200:79-87. 2004
    ..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...
  41. pmc NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression
    Devangi S Mehta
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:2016-21. 2005
    ..These data suggest that there are multiple mechanisms by which Th-cell-subset-specific cytokine genes are regulated...
  42. pmc A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells
    Greg H Underhill
    Department of Microbiology Immunology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611, USA
    Blood 106:3867-73. 2005
    ....
  43. ncbi Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
    Andrew M Intlekofer
    Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Immunol 6:1236-44. 2005
    ..Therefore, these key transcription factors link the long-term renewal of memory CD8(+) T cells to their characteristic effector potency...
  44. ncbi Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet
    Jianguo Xu
    Division of Pulmonary, Allergy, and Critical Care Medicine, Center for Translational Research of the Lung, Emory University School of Medicine, Atlanta, GA 30322, USA
    Am J Physiol Lung Cell Mol Physiol 291:L658-67. 2006
    ..These data suggest that the T-bet pathway in CD4+ T lymphocytes can confer resistance to BLM-induced lung fibrosis in BALB/c mice...
  45. pmc Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis
    Yi Chen
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304, USA
    J Clin Invest 116:1317-26. 2006
    ..Thus, therapeutic targeting of IL-23 effectively inhibited multiple inflammatory pathways that are critical for driving CNS autoimmune inflammation...
  46. pmc T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17
    Manu Rangachari
    Institute for Molecular Biotechnology of the Austrian Academy of Sciences, A 1030 Vienna, Austria
    J Exp Med 203:2009-19. 2006
    ..Collectively, these data show that severe IL-17-mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ...
  47. ncbi T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity
    Anne R Gocke
    Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Immunol 178:1341-8. 2007
    ..We now show for the first time that suppression of T-bet ameliorates EAE by limiting the differentiation of autoreactive Th1 cells, as well as inhibiting pathogenic Th17 cells via regulation of IL-23R...
  48. pmc Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells
    Andrew M Intlekofer
    Abramson Family Cancer Research Institute, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Exp Med 204:2015-21. 2007
    ..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...
  49. pmc Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor
    Nikhil S Joshi
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 27:281-95. 2007
    ..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...
  50. pmc Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system
    Wendy S Garrett
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Cell 131:33-45. 2007
    ..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...
  51. pmc T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis
    Richard K S Phoon
    Department of Medicine, Monash University, Monash Medical Centre, Level 5 Block E, 246 Clayton Road, Clayton, Victoria 3168, Australia
    J Am Soc Nephrol 19:477-85. 2008
    ..We conclude that T-bet directs Th1 responses that induce renal injury in experimental crescentic glomerulonephritis...
  52. ncbi Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation
    Shunsuke Furuta
    Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan
    J Immunol 180:6656-62. 2008
    ..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...
  53. pmc Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin
    Andrew M Intlekofer
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 321:408-11. 2008
    ..T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction...
  54. pmc The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions
    Damian Kovalovsky
    Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Immunol 9:1055-64. 2008
    ..PLZF, therefore, is an iNKT cell-specific transcription factor that is necessary for full functionality...
  55. pmc CD8+ Th17 mediate costimulation blockade-resistant allograft rejection in T-bet-deficient mice
    Bryna E Burrell
    Section of General Surgery, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    J Immunol 181:3906-14. 2008
    ....
  56. pmc Late developmental plasticity in the T helper 17 lineage
    Yun Kyung Lee
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Immunity 30:92-107. 2009
    ..These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense...
  57. pmc The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation
    Meghan A Koch
    Benaroya Research Institute, Seattle, Washington, USA
    Nat Immunol 10:595-602. 2009
    ....
  58. pmc c-Maf regulates IL-10 expression during Th17 polarization
    Jiangnan Xu
    Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Immunol 182:6226-36. 2009
    ..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...
  59. pmc T-bet is essential for encephalitogenicity of both Th1 and Th17 cells
    Yuhong Yang
    Department of Neurology, Ohio State University Medical Center, Columbus, OH 43210, USA
    J Exp Med 206:1549-64. 2009
    ..These data suggest that encephalitogenicity of myelin-specific T cells appears to be mediated by a pathway dependent on T-bet and not necessarily pathway-specific end products, such as interferon gamma and IL-17...
  60. pmc Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17
    Douglas M Durrant
    Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
    J Immunol 183:5293-300. 2009
    ..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...
  61. pmc Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection
    Guillaume Oldenhove
    Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 31:772-86. 2009
    ..These data reveal a mechanism for Th1 cell pathogenicity that extends beyond their proinflammatory program to limit Treg cell survival...
  62. doi The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin
    Rajesh R Rao
    Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Immunity 32:67-78. 2010
    ..Targeting mTOR activity offers new opportunities to regulate CD8+ T cell-mediated immunity...
  63. doi Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions
    Ahmed N Hegazy
    Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charite University Medicine Berlin, 10117 Berlin, Germany
    Immunity 32:116-28. 2010
    ..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...
  64. pmc Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells
    Matthew E Pipkin
    Harvard Medical School, Boston, MA 02115, USA Immune Disease Institute, Boston, MA 02115, USA
    Immunity 32:79-90. 2010
    ..Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development...
  65. pmc Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage
    Ryuta Mukasa
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Immunity 32:616-27. 2010
    ....
  66. pmc Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes
    Patrick Veiga
    Harvard School of Public Health, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:18132-7. 2010
    ..lactis-containing fermented milk product, and therefore this model provides a framework for evaluating and optimizing probiotic-based functional foods...
  67. pmc Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling
    Kamran Ghoreschi
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 467:967-71. 2010
    ..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...
  68. pmc STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms
    Alejandro V Villarino
    Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA
    J Immunol 185:6461-71. 2010
    ..Taken together, these studies formally establish that, downstream of IFN-γ, IL-27, and likely all STAT1-activating cytokines, there are both STAT1 and T-bet-dependent pathways capable of suppressing Th17 responses...
  69. pmc Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression
    Sara A Miller
    University of Washington, Seattle, WA 98195, USA
    Mol Cell 40:594-605. 2010
    ..This function for H3K27 demethylase proteins may explain their presence in differentiated cells where the epigenetic profile is already established...
  70. pmc T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt
    Vanja Lazarevic
    Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA
    Nat Immunol 12:96-104. 2011
    ..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...
  71. pmc Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages
    Wei Liao
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 12:551-9. 2011
    ..Thus, IL-2 influences helper T cell differentiation by modulating the expression of cytokine receptors to help specify and maintain differentiated states...
  72. pmc The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns
    Kenneth J Oestreich
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    J Exp Med 208:1001-13. 2011
    ....
  73. pmc c-Abl-mediated tyrosine phosphorylation of the T-bet DNA-binding domain regulates CD4+ T-cell differentiation and allergic lung inflammation
    An Chen
    Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Mol Cell Biol 31:3445-56. 2011
    ..Therefore, c-Abl catalyzes tyrosine phosphorylation of the DNA-binding domain of T-bet to regulate CD4(+) T cell differentiation...
  74. doi Overexpression of T-bet gene regulates murine autoimmune arthritis
    Yuya Kondo
    Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba City, Ibaraki, Japan
    Arthritis Rheum 64:162-72. 2012
    ..To clarify the role of T-bet in the pathogenesis of collagen-induced arthritis (CIA)...
  75. pmc Autoreactive Tbet-positive CD4 T cells develop independent of classic Th1 cytokine signaling during experimental autoimmune encephalomyelitis
    Wen I Yeh
    Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Immunol 187:4998-5006. 2011
    ..Th1 cytokine IFN-γ does not appear necessary for disease, but the key Th1-associated transcription factor Tbet has been reported to be essential for disease development...
  76. pmc Early Th1 cell differentiation is marked by a Tfh cell-like transition
    Shingo Nakayamada
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 35:919-31. 2011
    ..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...
  77. pmc The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation
    Scott M Gordon
    Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA
    Immunity 36:55-67. 2012
    ..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...
  78. pmc Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile
    Kenneth J Oestreich
    Department of Immunology, University of Washington, Seattle, Washington, USA
    Nat Immunol 13:405-11. 2012
    ..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...
  79. pmc TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells
    Hayato Takahashi
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 13:587-95. 2012
    ..We also found that miR-10a limited differentiation into the T(H)17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells...
  80. pmc The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses
    Jinfang Zhu
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 37:660-73. 2012
    ..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...
  81. pmc The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells
    Nick Powell
    Department of Experimental Immunobiology, Division of Transplantation Immunology and Mucosal Biology, King s College London, UK
    Immunity 37:674-84. 2012
    ..interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice...
  82. pmc Distinct requirements for T-bet in gut innate lymphoid cells
    Giuseppe Sciumè
    Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 209:2331-8. 2012
    ..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 ..
  83. pmc T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements
    Aditi Kanhere
    Division of Infection and Immunity and UCL Cancer Institute, University College London, London WC1E 6BT, UK
    Nat Commun 3:1268. 2012
    ..Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression...
  84. doi A T-bet gradient controls the fate and function of CCR6-RORγt+ innate lymphoid cells
    Christoph S N Klose
    Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann Herder Strasse 11, D 79104 Freiburg, Germany
    Nature 494:261-5. 2013
    ....
  85. ncbi Asthmatic changes in mice lacking T-bet are mediated by IL-13
    Susetta Finotto
    Laboratory of Cellular and Molecular Immunology of the Lung, University of Mainz, Mainz, Germany
    Int Immunol 17:993-1007. 2005
    ..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...
  86. pmc IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508
    Eun Sook Hwang
    Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul, Korea
    J Exp Med 202:1289-300. 2005
    ..Heterodimerization of T-bet and RelA interferes with the binding of RelA to the IL-2 promoter, and hence, transcriptional activation of the IL-2 gene by RelA...
  87. pmc T-bet is essential for the progression of experimental autoimmune encephalomyelitis
    Narender Nath
    Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA
    Immunology 118:384-91. 2006
    ..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...
  88. ncbi T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity
    Viviany R Taqueti
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 177:5890-901. 2006
    ..These findings highlight the potential therapeutic benefit of targeting T-bet-regulated gene expression and CXCR3-dependent migration in immune-mediated heart disease...
  89. ncbi T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis
    Olof H Hultgren
    Department of Clinical Immunology, Göteborg University Gulhedsgatan 10A S 413 46 Göteborg, Sweden
    Microbes Infect 6:529-35. 2004
    ..aureus infection, protecting against bacterial accumulation, cachexia and septic death. Furthermore T-bet downregulates joint inflammation in the early phase of disease...
  90. pmc T-bet concomitantly controls migration, survival, and effector functions during the development of Valpha14i NKT cells
    Jennifer L Matsuda
    Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, CO, USA
    Blood 107:2797-805. 2006
    ....
  91. pmc Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells
    Anja Fuchs
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 38:769-81. 2013
    ..In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3- and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are ..
  92. pmc The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway
    Lucille C Rankin
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Nat Immunol 14:389-95. 2013
    ..We report here that the transcription factor T-bet (encoded by Tbx21) was essential for the development of NKp46+ ILCs but not of LTi cells or nuocytes...
  93. ncbi The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons
    Ronald R Waclaw
    Division of Developmental Biology, Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Neuron 49:503-16. 2006
    ....
  94. ncbi STAT1 in peripheral tissue differentially regulates homing of antigen-specific Th1 and Th2 cells
    Zamaneh Mikhak
    Division of Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 176:4959-67. 2006
    ....
  95. ncbi Cutting edge: STAT1 and T-bet play distinct roles in determining outcome of visceral leishmaniasis caused by Leishmania donovani
    Lucia E Rosas
    Department of Microbiology, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
    J Immunol 177:22-5. 2006
    ..These unexpected findings reveal distinct roles for T-bet and STAT1 in mediating host immunity and liver pathology during visceral leishmaniasis...
  96. pmc Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals
    Haruyuki Ariga
    Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Immunology 122:210-21. 2007
    ....
  97. pmc IL-7 receptor expression provides the potential for long-term survival of both CD62Lhigh central memory T cells and Th1 effector cells during Leishmania major infection
    Sara L Colpitts
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 182:5702-11. 2009
    ..Thus, both T(CM) and Th1 effector cells can express the IL7R during chronic L. major infection, which provides a potential means for their long-term survival in addition to the presence of persisting parasites...
  98. pmc A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells
    Yonghua Zhuang
    Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA
    Immunology 128:34-42. 2009
    ..Additionally, we found that T-bet is required to maintain Ifng expression. Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential...
  99. doi Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma
    Michael Hausding
    Laboratory of Cellular and Molecular Immunology of Lung, Institute of Molecular Medicine, Universitätsmedizin Mainz, 55131 Mainz, Germany
    Int Immunol 23:1-15. 2011
    ..Thus, GL treatment in vivo and in vitro emerges as a novel therapeutic approach for allergic asthma by modulating lung DC phenotype and function resulting in a protective response via CD4(+)FoxP3(+) regulatory T cells locally...
  100. pmc Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice
    Marcel Wuthrich
    Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    J Clin Invest 121:554-68. 2011
    ..These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective...
  101. pmc Stat4 is critical for the balance between Th17 cells and regulatory T cells in colitis
    Jiangnan Xu
    Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Immunol 186:6597-606. 2011
    ..These results highlight the critical role of Stat4 Th1 signals in autoimmune responses in suppressing Foxp3(+) Treg responses and altering the balance between Th17 and Tregs to favor autoimmune disease...

Research Grants2

  1. Recombinant murine IL-10 produced in situ by H. pylori
    KATHRYN EATON; Fiscal Year: 2005
    ..pylori, but will also establish a model in which the roles of other cytokines and mediators can be determined, and host and bacterial interactions can be directly evaluated in vivo. ..
  2. Host and Bacterial Factors in Disease due to H. pylori
    Kathryn A Eaton; Fiscal Year: 2010
    ..This will allow us to hire additional staff to ensure rapid completion of the remaining experiments. With these changes we fully expect to complete these experiments in 2 years. ..