Disease relevance of Tbx21

• We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D [1].
• T-bet regulates metastasis rate in a murine model of primary prostate cancer [2].
• T-bet deficiency facilitates airway colonization by Mycoplasma pulmonis in a murine model of asthma [3].
• These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis [4].
• These Tg mice, which overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by swollen, flaky, and scaly skin in regions without body hair [4].
• T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence of adaptive immunity and increased susceptibility to colitis in immunologically intact hosts [5].
• Adoptive transfer of wild-type activated NK cells protects T-bet(-/-) animals after melanoma challenge showing that reconstitution of the NK compartment in these mice is sufficient to mediate a significant reduction in tumor burden [6].

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

• The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease [11].
• The effects of allitridin on the expression of transcription factors T-bet and GATA-3 in mice infected by murine cytomegalovirus [12].
• Allergen-induced goblet cell hyperplasia and mucus hypersecretion were significantly lower in mice overexpressing T-bet than in wild-type mice [13].

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

• T-bet/Tbx21 expression is exclusively restricted to the olfactory bulb and the thymus [17].
• Under these same stimulation conditions, Itk-/- T cells produce large amounts of T-bet mRNA and differentiate into IFN-gamma-producing cells [10].
• T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes [1].
• Further, T-bet expression in DCs is required for T helper cell activation [18].
• Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells [18].

Associations of Tbx21 with chemical compounds

• The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-gamma production by DCs [18].
• During a 15-d exposure to progesterone, T-bet levels in endometrial epithelial cells (EECs) undulated [19].
• Regulation of T-bet expression was modulated by cytokines and the female reproductive steroids, estrogen, and progesterone [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 [19].
• Here we report that CpG, but not lipopolysaccharide (LPS), rapidly induces expression of T-bet mRNA in purified B cells [20].

Physical interactions of Tbx21

• Here we show that in the absence of T-box expressed in T cells (T-bet), selective migration of T cells in vivo is completely abrogated and that T-bet regulates the binding of CD4(+) T cells to P-selectin [21].

Regulatory relationships of Tbx21

• Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation [22].
• Here we report that Notch1 can directly regulate Tbx21 through complexes formed on the Tbx21 promoter [14].
• AIM: To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice [23].
• LLO treatment resulted in a reduction of GATA-3 and SOCS-3 expressions but induced the transcription of T-bet instead [24].
• The IL-27-induced IgG2a class switching is highly dependent on T-bet in response to T-independent stimuli such as LPS [25].
• These findings highlight the potential therapeutic benefit of targeting T-bet-regulated gene expression and CXCR3-dependent migration in immune-mediated heart disease [26].
• Luciferase reporter assay showed that both Stat4 and Stat1 activate reporter gene expression from constructs containing a wild-type but not mutated T-bet enhancer [27].

Other interactions of Tbx21

• T-bet-dependent expression of osteopontin contributes to T cell polarization [28].
• To clarify how helper T cell subset differentiation influences atherosclerosis, we compared lesion development and immune responses to plaque antigens in low-density lipoprotein receptor-deficient (Ldlr-/-) mice with or without functional T-bet genes [29].
• IL-27 is a novel IL-12 family member that plays a role in the early regulation of T helper cell 1 initiation, including induction of T-bet and IL-12 receptor beta 2 expression [30].
• We demonstrate decreased T-bet expression and significantly reduced IgG1 and IgG2a anti-collagen II Ab levels in PKC-theta-deficient mice [31].
• Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells [32].

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].

References