T-bet protein, also known as TBX21, is a transcription factor that regulates gene transcription, thereby influencing the development and function of immune cells. It plays a pivotal role in the immune system, particularly in regulating the differentiation and function of Th1 cells. As a Th1-specific transcription factor, T-bet induces the production of interferon-γ (IFN-γ), playing a decisive role in the differentiation of Th1 cells. It serves as a powerful transcriptional activator of the IFN-γ gene while also inducing and maintaining the expression of IL-12Rβ2. Additionally, T-bet can convert differentiating effector Th2 cells and fully differentiated Th2 cells into Th1 cells, accompanied by the production of large amounts of IFN-γ and the suppression of Th2-type cytokines such as IL-4, IL-5, and IL-13. During T-cell activation, T-bet expression is upregulated by IFN-γ. However, transforming growth factor-β (TGF-β) can suppress T-bet through a STAT1-dependent pathway, thereby inhibiting the differentiation of Th1 cells. Due to T-bet's crucial role in Th1 cell development and function, its activity is essential for maintaining normal immune system function. Th1 cells primarily participate in immune responses against intracellular pathogens, thus highlighting the significance of T-bet in protecting the body against such pathogens. However, abnormal TBX21 gene expression or function may be associated with immune system-related diseases, such as autoimmune disorders or immunodeficiencies.
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