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Gene Review

Tbx21  -  T-box 21

Mus musculus

Synonyms: T-bet, T-box protein 21, T-box transcription factor TBX21, T-cell-specific T-box transcription factor T-bet, TBT1, ...
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Disease relevance of Tbx21


High impact information on Tbx21

  • A novel transcription factor, T-bet, directs Th1 lineage commitment [7].
  • T-bet expression correlates with IFNgamma expression in Th1 and NK cells [7].
  • Role of T-bet in commitment of TH1 cells before IL-12-dependent selection [8].
  • Interestingly, in addition to its expression on DCs, Sema4A is upregulated on Th1-differentiating cells, and it is necessary for in vitro Th1 differentiation and T-bet expression [9].
  • Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet [10].

Chemical compound and disease context of Tbx21


Biological context of Tbx21

  • Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21 [14].
  • In addition to the human cDNA sequence, we report the cDNA sequence of the murine homologue, the structure and organization of the murine Tbx21 gene, and its localization to mouse chromosome 11 [15].
  • By constructing a dominant-negative form of T-bet, we were able to determine the role played by this lineage-inducing trans-activator in the establishment and maintenance of heritable T(H)1 gene expression [16].
  • In fully mature T(H)1 cells, reiteration of IFN-gamma expression and stable chromatin remodeling became relatively independent of T-bet activity and coincided with demethylation of DNA [16].
  • Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes [1].

Anatomical context of Tbx21


Associations of Tbx21 with chemical compounds


Physical interactions of Tbx21


Regulatory relationships of Tbx21


Other interactions of Tbx21


Analytical, diagnostic and therapeutic context of Tbx21

  • Moreover, the antitumor activity was abolished in T-bet-deficient mice, whereas it was observed unexpectedly in mice deficient of signal transducer and activator of transcription (STAT) 4 [30].
  • We have used in situ hybridization to determine the temporal and spatial distribution of T-bet/Tbx21 expression during mouse development [17].
  • Colon tissue was analyzed macroscopically and microscopically, myeloperoxidase activity and cytokine levels [tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-10, and IL-4] were determined by enzyme-linked immunosorbent assay, and T-box transcription factor (T-bet) expression was determined by immunoblot analysis [33].
  • We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively [11].
  • A Salmonella-specific TCR transgenic adoptive transfer system was used to further define the involvement of T-bet expression in the development of Salmonella-specific Th1 cells [34].


  1. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. Juedes, A.E., Rodrigo, E., Togher, L., Glimcher, L.H., von Herrath, M.G. J. Exp. Med. (2004) [Pubmed]
  2. T-bet regulates metastasis rate in a murine model of primary prostate cancer. Peng, S.L., Townsend, M.J., Hecht, J.L., White, I.A., Glimcher, L.H. Cancer Res. (2004) [Pubmed]
  3. T-bet deficiency facilitates airway colonization by Mycoplasma pulmonis in a murine model of asthma. Bakshi, C.S., Malik, M., Carrico, P.M., Sellati, T.J. J. Immunol. (2006) [Pubmed]
  4. Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis. Ishizaki, K., Yamada, A., Yoh, K., Nakano, T., Shimohata, H., Maeda, A., Fujioka, Y., Morito, N., Kawachi, Y., Shibuya, K., Otsuka, F., Shibuya, A., Takahashi, S. J. Immunol. (2007) [Pubmed]
  5. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Garrett, W.S., Lord, G.M., Punit, S., Lugo-Villarino, G., Mazmanian, S.K., Ito, S., Glickman, J.N., Glimcher, L.H. Cell (2007) [Pubmed]
  6. T-bet plays a key role in NK-mediated control of melanoma metastatic disease. Werneck, M.B., Lugo-Villarino, G., Hwang, E.S., Cantor, H., Glimcher, L.H. J. Immunol. (2008) [Pubmed]
  7. A novel transcription factor, T-bet, directs Th1 lineage commitment. Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Fathman, C.G., Glimcher, L.H. Cell (2000) [Pubmed]
  8. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Mullen, A.C., High, F.A., Hutchins, A.S., Lee, H.W., Villarino, A.V., Livingston, D.M., Kung, A.L., Cereb, N., Yao, T.P., Yang, S.Y., Reiner, S.L. Science (2001) [Pubmed]
  9. Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Kumanogoh, A., Shikina, T., Suzuki, K., Uematsu, S., Yukawa, K., Kashiwamura, S., Tsutsui, H., Yamamoto, M., Takamatsu, H., Ko-Mitamura, E.P., Takegahara, N., Marukawa, S., Ishida, I., Morishita, H., Prasad, D.V., Tamura, M., Mizui, M., Toyofuku, T., Akira, S., Takeda, K., Okabe, M., Kikutani, H. Immunity (2005) [Pubmed]
  10. Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet. Miller, A.T., Wilcox, H.M., Lai, Z., Berg, L.J. Immunity (2004) [Pubmed]
  11. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. Neurath, M.F., Weigmann, B., Finotto, S., Glickman, J., Nieuwenhuis, E., Iijima, H., Mizoguchi, A., Mizoguchi, E., Mudter, J., Galle, P.R., Bhan, A., Autschbach, F., Sullivan, B.M., Szabo, S.J., Glimcher, L.H., Blumberg, R.S. J. Exp. Med. (2002) [Pubmed]
  12. The effects of allitridin on the expression of transcription factors T-bet and GATA-3 in mice infected by murine cytomegalovirus. Yi, X., Feng, F., Xiang, Z., Ge, L. Journal of medicinal food. (2005) [Pubmed]
  13. Transcription factors T-bet and GATA-3 regulate development of airway remodeling. Kiwamoto, T., Ishii, Y., Morishima, Y., Yoh, K., Maeda, A., Ishizaki, K., Iizuka, T., Hegab, A.E., Matsuno, Y., Homma, S., Nomura, A., Sakamoto, T., Takahashi, S., Sekizawa, K. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  14. Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21. Minter, L.M., Turley, D.M., Das, P., Shin, H.M., Joshi, I., Lawlor, R.G., Cho, O.H., Palaga, T., Gottipati, S., Telfer, J.C., Kostura, L., Fauq, A.H., Simpson, K., Such, K.A., Miele, L., Golde, T.E., Miller, S.D., Osborne, B.A. Nat. Immunol. (2005) [Pubmed]
  15. Cloning and characterization of a new member of the T-box gene family. Zhang, W.X., Yang, S.Y. Genomics (2000) [Pubmed]
  16. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction. Mullen, A.C., Hutchins, A.S., High, F.A., Lee, H.W., Sykes, K.J., Chodosh, L.A., Reiner, S.L. Nat. Immunol. (2002) [Pubmed]
  17. Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis. Faedo, A., Ficara, F., Ghiani, M., Aiuti, A., Rubenstein, J.L., Bulfone, A. Mech. Dev. (2002) [Pubmed]
  18. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. Wang, J., Fathman, J.W., Lugo-Villarino, G., Scimone, L., von Andrian, U., Dorfman, D.M., Glimcher, L.H. J. Clin. Invest. (2006) [Pubmed]
  19. 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. Kawana, K., Kawana, Y., Schust, D.J. Mol. Endocrinol. (2005) [Pubmed]
  20. CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Liu, N., Ohnishi, N., Ni, L., Akira, S., Bacon, K.B. Nat. Immunol. (2003) [Pubmed]
  21. T-bet is required for optimal proinflammatory CD4+ T-cell trafficking. Lord, G.M., Rao, R.M., Choe, H., Sullivan, B.M., Lichtman, A.H., Luscinskas, F.W., Glimcher, L.H. Blood (2005) [Pubmed]
  22. T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells. Afkarian, M., Sedy, J.R., Yang, J., Jacobson, N.G., Cereb, N., Yang, S.Y., Murphy, T.L., Murphy, K.M. Nat. Immunol. (2002) [Pubmed]
  23. Effects of CpG oligodeoxynucleotide on transcription factors GATA-3 and T-bet mRNA expression in asthmatic mice. Wu, Z.Q., Xu, Y.P., Xiang, H., Shen, H.H. Acta Pharmacol. Sin. (2005) [Pubmed]
  24. Listeriolysin O, a cytolysin derived from Listeria monocytogenes, inhibits generation of ovalbumin-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells. Yamamoto, K., Kawamura, I., Tominaga, T., Nomura, T., Kohda, C., Ito, J., Mitsuyama, M. Clin. Exp. Immunol. (2005) [Pubmed]
  25. Induction of IgG2a class switching in B cells by IL-27. Yoshimoto, T., Okada, K., Morishima, N., Kamiya, S., Owaki, T., Asakawa, M., Iwakura, Y., Fukai, F., Mizuguchi, J. J. Immunol. (2004) [Pubmed]
  26. T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity. Taqueti, V.R., Grabie, N., Colvin, R., Pang, H., Jarolim, P., Luster, A.D., Glimcher, L.H., Lichtman, A.H. J. Immunol. (2006) [Pubmed]
  27. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Yang, Y., Ochando, J.C., Bromberg, J.S., Ding, Y. Blood (2007) [Pubmed]
  28. T-bet-dependent expression of osteopontin contributes to T cell polarization. Shinohara, M.L., Jansson, M., Hwang, E.S., Werneck, M.B., Glimcher, L.H., Cantor, H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses. Buono, C., Binder, C.J., Stavrakis, G., Witztum, J.L., Glimcher, L.H., Lichtman, A.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  30. Potent antitumor activity of interleukin-27. Hisada, M., Kamiya, S., Fujita, K., Belladonna, M.L., Aoki, T., Koyanagi, Y., Mizuguchi, J., Yoshimoto, T. Cancer Res. (2004) [Pubmed]
  31. PKC-theta-deficient mice are protected from Th1-dependent antigen-induced arthritis. Healy, A.M., Izmailova, E., Fitzgerald, M., Walker, R., Hattersley, M., Silva, M., Siebert, E., Terkelsen, J., Picarella, D., Pickard, M.D., LeClair, B., Chandra, S., Jaffee, B. J. Immunol. (2006) [Pubmed]
  32. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Szabo, S.J., Sullivan, B.M., Stemmann, C., Satoskar, A.R., Sleckman, B.P., Glimcher, L.H. Science (2002) [Pubmed]
  33. The new low calcemic vitamin d analog 22-ene-25-oxa-vitamin d prominently ameliorates T helper cell type 1-mediated colitis in mice. Daniel, C., Radeke, H.H., Sartory, N.A., Zahn, N., Zuegel, U., Steinmeyer, A., Stein, J. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  34. Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. Ravindran, R., Foley, J., Stoklasek, T., Glimcher, L.H., McSorley, S.J. J. Immunol. (2005) [Pubmed]
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