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FLASH GENE
Symbol TBX21 contributors: mct - updated : 27-03-2017
HGNC name T-box 21
HGNC id 11599
Location 17q21.32      Physical location : 45.810.609 - 45.823.485
Synonym name
  • T-box expressed in T cells
  • T-cell-specific T-box transcription factor
  • transcription factor TBLYM
    • Synonym symbol(s) TBLYM, T-PET, T-BET, TBET
    DNA
    TYPE functioning gene
    STRUCTURE 12.88 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2589 - 535 - 2000 11087660
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen    
     thymus    
    Reproductivefemale systemuterus  highly
    Respiratorylung    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Reproductiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one T-box DNA binding domain
    • HOMOLOGY
    interspecies homolog to murine Tbx21 (87.9pc)
    homolog to rattus Tbx21 (87.7pc)
    Homologene
    FAMILY T box family
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text expressed in endometrial epithelium cyclically during the menstrual cycle (Inman 2008)
    basic FUNCTION
  • regulating lineage commitment in CD4 T helper (TH) lymphocytes
  • inducing the expression of endogenous IFNgamma in non-immune human cells, independently of its role in T-cell lineage determination
  • involed in the regulation of developmental processes
  • may be involved in initiating Th1 lineage development for naive Th precursor cells
  • transcription factor that controls the expression of the Th1 cytokine, IFNG
  • initiates Th1 lineage development from naive TH precursor cells both by activating TH1 genetic programs and by repressing the opposing TH2 programs
  • with GATA3 regulate cytokine expression in T-lymphocytes (Inman 2008)
  • novel mechanism for TBX21-mediated gene repression in which two lineage-defining transcription factors, one a classical activator and one a repressor, collaborate to promote and properly regulate Th1 development
  • is essential for establishing Th1-mediated inflammation but is not required to drive IL23-induced CSF2 production, or Th17-mediated autoimmune inflammation
  • during the differentiation process NK cells gradually display increasing expression of IFNG and TBX21 (encoding T-bet) transcripts and demethylation at the IFNG promoter
  • plays multiple roles in many subtypes of immune cells, including B cell, dendritic cells, natural killer (NK) cells, NK T cells, and innate lymphoid cells
  • regulates intraepithelial lymphocyte functional maturation
  • given the essential function of TBX21 in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21
  • activated Treg cells transiently upregulated either TBX21 or GATA3 to maintain T cell homeostasis
  • regulatory pathway by which the negative regulator FOXO1 and the positive regulator TBX21 play opposing roles in controlling NK cell development and effector functions
  • regulates natural regulatory T cells (nTreg) migration into afferent lymphatics and draining lymph nodes (dLN) and consequently their suppressive stability
    • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding through T-box
    RNA
    small molecule
    protein
  • interacting with IFNG (role in the development of the diabetes)
  • transactivates ONECUT2 transcription through putative TBX21 half-sites locating -451 to -347 of OC2 promoter region
  • HAVCR2 expression is regulated by the Th1-specific transcription factor TBX21
  • IL36G, besides IFNG may contribute to functions of TBX21 transcription factor in immunopathology
  • IL21 drives CD8(+) CTL differentiation via the actions of the transcription factor TBX21
  • signaling cascades driven by the BCR and TLR9 have a newly identified meeting point at TBX21
  • directly activates IFNG1 gene transcription and enhances development of Th1 cells
  • cooperation between the transcription factors TBX21 and RUNX3 resulted in suppression of conventional CD4(+) T helper functions and induction of an intraepithelial lymphocyte (IEL) program
  • TOX2 was independent of ETS1 but could directly upregulate the transcription of TBX21 (encoding T-BET)
  • BHLHE40 works as a cofactor of TBX21 for enhancing IFNG1 production in invariant natural killer T (iNKT) cells
    • cell & other
    REGULATION
    induced by EGR1 in activated T cells (Shin 2009)
    repressed by the transcriptional repressor Ikaros (Thomas 2010)
    Other expression at a naive stage is crucial for the development of IFNG-producing T cells in peripheral blood, even in Th2-related diseases (Kaminuma 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    during the late secretory phase in the endometrium, suggesting antagonistic function and/or regulation between progesterone receptor and TBX21/GATA3 (Inman 2008)
    constitutional     --over  
    in active Immune thrombocytopenia (ITP) patients compared to control
    constitutional     --over  
    induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung
    Susceptibility
  • to insulin dependent type 1 diabetes
  • to asthma resistant to inhaled corticosteroids
  • to aspirin-induced ashma
    • Variant & Polymorphism SNP
  • His33>Gln associated with type 1 diabetes
  • His33>Gln associated with asthma resistant to inhaled corticosteroids
  • 1993T>C associated with aspirin-induced asthma
  • SNPs in TBX21 increase the risk of systemic sclerosis (Gourh 2009)
  • T1993C polymorphism in the TBX21 promoter influences susceptibility to persistent HBV infection (Chen 2009)
  • TBX21 T-1993C polymorphism represses TBX21 expression and Th1 cytokine production through control of YY1, which might result in the imbalance between Th1 and Th2 immune responses in autoimmune or allergic diseases
    • Candidate gene
  • can be considered as putative marker of chronic inflammatory demyelinating polyradiculoneuropathy (Shin 2009)
    • Marker
    Therapy target
  • for the treatment of systemic sclerosis and other fibrosing disorders
    • ANIMAL & CELL MODELS
  • mice lacking both transcription factors Eomesodermin (Eomes) and Tbx21 failed to develop NK cells