TBX21
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T-bet
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| Location (UCSC) | Chr 17: 47.73 – 47.75 Mb | Chr 11: 96.99 – 97.01 Mb | |||||||
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T-box transcription factor TBX21, also called T-bet (T-box expressed in T cells) is a protein that in humans is encoded by the TBX21 gene.[5] Though being for long thought of only as a master regulator of type 1 immune response, T-bet has recently been shown to be implicated in development of various immune cell subsets and maintenance of mucosal homeostasis.[6]
Function
This gene is a member of a phylogenetically conserved family of genes that share a common
IFNg). Expression of the human ortholog also correlates with IFNg expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells.[5]
The function of T-bet is best known in
Th17). In a typical scenario it is thought that IFNg and T cell receptor (TCR) signalling initiates the expression of Tbet, and once TCR signalling stops, signalling via IL-12 receptor can come to play as it was blocked by repression of expression of one of its receptor subunits (IL12Rb2) by TCR signalling. IL-2 signalling enhances the expression of IL-12R. The 2-step expression of T-bet can be viewed as a safety mechanism of sort, which ensures, that cells commit to the Th1 phenotype only when desired.[6]
T-bet controls transcription of many genes, for example proinflammatory cytokines like lymphotoxin-a, tumour necrosis factor and ifng, which is a hallmark cytokine of type one immunity.
Apart from promoting type 1 immune response (
Th17) phenotype is suppressed by RUNX1 recruitment, which disallows it to mediate Th17 specific genes, like rorc, a Th17 master regulator. Rorc is also silenced by epigenetic changes promoted by T-bet and STAT4.[6]
T-bet also performs function in
Role in mucosal homeostasis
It has been identified that T-bet contributes to the maintenance of mucosal homeostasis and mucosal immune response. Mice lacking adapative immune cells and T-bet (
dendritic cells and immune system is more biased away from Th1.[9]
Role in disease
Atherosclerosis
antigens by cytotoxic T cells and increased differentiation of TREGs suppressing immune response. Taken together T-bet might serve as a potential target in treatment of atherosclerosis.[7]
Asthma
The transcription factor encoded by TBX21 is T-bet, which regulates the development of naive T lymphocytes. Asthma is a disease of chronic inflammation, and it is known that transgenic mice born without TBX21 spontaneously develop abnormal lung function consistent with asthma. It is thought that TBX21, therefore, may play a role in the development of asthma in humans as well.[10]
Experimental autoimmune encephalomyelitis
Initially it was thought that
cytotoxic T cells, downregulates T cell trafficking and limits their survival. T-bet and its controlled genes remain a possible target in treatment of neurological autoimmune diseases.[12]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000073861 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001444 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: TBX21 T-box 21".
- ^ PMID 24113868.
- ^ S2CID 54473768.
- PMID 30874358.
- PMID 26726991.
- PMID 15604153.
- PMID 19132915.
- PMID 35909230.
Further reading
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. PMID 9373149.
- Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (March 2000). "A novel transcription factor, T-bet, directs Th1 lineage commitment". Cell. 100 (6): 655–669. S2CID 14326322.
- Zhang WX, Yang SY (November 2000). "Cloning and characterization of a new member of the T-box gene family". Genomics. 70 (1): 41–48. PMID 11087660.
- Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein JL, Bulfone A (August 2002). "Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis". Mechanisms of Development. 116 (1–2): 157–160. S2CID 14925626.
- Chung HT, Kim LH, Park BL, Lee JH, Park HS, Choi BW, et al. (September 2003). "Association analysis of novel TBX21 variants with asthma phenotypes". Human Mutation. 22 (3): 257. S2CID 21977810.
- Yu HR, Chang JC, Chen RF, Chuang H, Hong KC, Wang L, Yang KD (November 2003). "Different antigens trigger different Th1/Th2 reactions in neonatal mononuclear cells (MNCs) relating to T-bet/GATA-3 expression". Journal of Leukocyte Biology. 74 (5): 952–958. S2CID 39107628.
- Lametschwandtner G, Biedermann T, Schwärzler C, Günther C, Kund J, Fassl S, et al. (May 2004). "Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities". The Journal of Allergy and Clinical Immunology. 113 (5): 987–994. PMID 15131585.
- Sasaki Y, Ihara K, Matsuura N, Kohno H, Nagafuchi S, Kuromaru R, et al. (August 2004). "Identification of a novel type 1 diabetes susceptibility gene, T-bet". Human Genetics. 115 (3): 177–184. S2CID 32348097.
- Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, et al. (December 2004). "TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids". Proceedings of the National Academy of Sciences of the United States of America. 101 (52): 18099–18104. PMID 15604153.
- Atayar C, Poppema S, Blokzijl T, Harms G, Boot M, van den Berg A (January 2005). "Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas". The American Journal of Pathology. 166 (1): 127–134. PMID 15632006.
- Tong Y, Aune T, Boothby M (February 2005). "T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site". Proceedings of the National Academy of Sciences of the United States of America. 102 (6): 2034–2039. PMID 15684083.
- Dorfman DM, Hwang ES, Shahsafaei A, Glimcher LH (January 2005). "T-bet, a T cell-associated transcription factor, is expressed in Hodgkin's lymphoma". Human Pathology. 36 (1): 10–15. PMID 15712176.
- Kulkarni A, Ravi DS, Singh K, Rampalli S, Parekh V, Mitra D, Chattopadhyay S (April 2005). "HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response". Biochemical and Biophysical Research Communications. 329 (2): 706–712. PMID 15737643.
- Akahoshi M, Obara K, Hirota T, Matsuda A, Hasegawa K, Takahashi N, et al. (June 2005). "Functional promoter polymorphism in the TBX21 gene associated with aspirin-induced asthma". Human Genetics. 117 (1): 16–26. S2CID 23920947.
- Kawana K, Kawana Y, Schust DJ (August 2005). "Female steroid hormones use signal transducers and activators of transcription protein-mediated pathways to modulate the expression of T-bet in epithelial cells: a mechanism for local immune regulation in the human reproductive tract". Molecular Endocrinology. 19 (8): 2047–2059. S2CID 31585846.
- Harashima A, Matsuo Y, Drexler HG, Okochi A, Motoda R, Tanimoto M, Orita K (July 2005). "Transcription factor expression in B-cell precursor-leukemia cell lines: preferential expression of T-bet". Leukemia Research. 29 (7): 841–848. PMID 15927679.
- Deng Y, Kerdiles Y, Chu J, Yuan S, Wang Y, Chen X, et al. (March 2015). "Transcription factor Foxo1 is a negative regulator of natural killer cell maturation and function". Immunity. 42 (3): 457–470. PMID 25769609.
- Raby BA, Hwang ES, Van Steen K, Tantisira K, Peng S, Litonjua A, et al. (January 2006). "T-bet polymorphisms are associated with asthma and airway hyperresponsiveness". American Journal of Respiratory and Critical Care Medicine. 173 (1): 64–70. PMID 16179640.
External links
- TBX21+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)