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. 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. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human ortholog of mouse Tbx21/Tbet gene. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (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.
Background References
1. Yang X et al. TBX21 inhibits colorectal cancer metastasis through ARHGAP29/GSK3beta inhibitory signaling- and MYCT1/ZO-1 signaling-dependent manner. Int J Biol Sci. 2025 Jan
2. Zou Z et al. TBX21 knockdown attenuates neuroinflammation induced by intracerebral hemorrhage via the SIRT1-WDR5-H3K4me3 axis. Brain Res Bull. 2025 Sep
Tissue Specificity
T-cell specific. Expressed in regulatory T (TReg) cells.
Post-translational Modification
Phosphorylations at Ser-52, Tyr-76, Ser-224 and Ser-508 are regulated by mTORC1. Phosphorylation at Tyr-525 is essential for its interaction GATA3. Phosphorylation at Tyr-219, Tyr-265 and Tyr-304 enhances its transcriptional activator activity. Phosphorylation at Thr-302 is required for its interaction with NFATC2.; Ubiquitinated at Lys-313, leading to its degradation by the proteasome. Ubiquitination is essential for controlling protein stability, binding to the T-box-binding element of the IFN-gamma promoter, and for interaction with NFATC2 through induction of phosphorylation at Thr-302. Deubiquitinated by USP10 leading to its stabilization (By similarity).
Western blot analysis of T-bet / Tbx21 on NK-92 cell lysates with Rabbit anti-T-bet / Tbx21 antibody (ER1802-65) at 1/2,000 dilution.
Lysates/proteins at 20 µg/Lane.
Predicted band size: 58 kDa Observed band size: 65 kDa
Exposure time: 1 minute; ECL: K1801;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (ER1802-65) at 1/2,000 dilution was used in primary antibody dilution (K1803) at 4℃ overnight. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1/50,000 dilution was used for 1 hour at room temperature.
Flow cytometric analysis of Raji cells labeling T-bet / Tbx21.
Cells were fixed and permeabilized. Then stained with the primary antibody (ER1802-65, 1ug/ml) (red) compared with Rabbit IgG Isotype Control (green). After incubation of the primary antibody at +4℃ for an hour, the cells were stained with a iFluor™ 488 conjugate-Goat anti-Rabbit IgG Secondary antibody (HA1121) at 1/1,000 dilution for 30 minutes at +4℃. Unlabelled sample was used as a control (cells without incubation with primary antibody; black).
Immunohistochemical analysis of paraffin-embedded human lymph nodes tissue with Rabbit anti-T-bet / Tbx21 antibody (ER1802-65) at 1/500 dilution.
The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) (high pressure) for 2 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ER1802-65) at 1/500 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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