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FLASH GENE

Symbol

TBX21

contributors: mct - updated : 27-03-2017

HGNC name	T-box 21
HGNC id	11599

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen           thymus         Reproductive female system uterus     highly Respiratory lung

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte Reproductive epithelial 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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