T-bet
Synonym(s)
HistoryThis section has been translated automatically.
Szabo, Glimcher 2000
DefinitionThis section has been translated automatically.
T-cell-specific transcription factor from the T-box gene family, which is encoded by the TBX21 gene (TBX21 stands for: T-box transcription factor 21) on chromosome 17. The defining part of this transcription factor is a highly conserved sequence called the T-box . T-bet acts as the key regulator of the Th1 response and is responsible for controlling the production of IFN-gamma . It is controlled via a negative feedback mechanism with IFN-gamma.
General informationThis section has been translated automatically.
When a naive CD4 T lymphocyte recognizes an antigen (e.g. a pathogenic germ) in the presence of IFN-gamma, a coordinated signalling cascade is set in motion via the activation of the T cell receptor and STAT1. This leads to increased expression of T-bet. This induces the formation of IL12 with consecutive activation of STAT-4. T-bet not only controls the production of IFN-gamma, but also influences the Th2 cells in a kind of inverse feedback loop.
Functional silencing of the coding TBX21 gene leads to a very low production of IFN-gamma when CD4 cells are stimulated under conditions that elicit a Th1 response, but to a significant increase in Th2 cytokines such as IL4 and IL5.
The master regulator of the Th2 response, on the other hand, is GATA 3. The balance between T-bet and GATA3 is important for a balanced immune response. Disturbances of this homeostasis are observed in various diseases. Disorders of this homeostasis are observed in various diseases, such as type I allergies and numerous autoimmune diseases.
LiteratureThis section has been translated automatically.
- Domeier PP et al. (2016) IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J Exp Med 213:715-732.
- Elbendary A et al. (2016) Expression of T-bet and GATA-3 in early mycosis fungoides and spongiotic dermatitis. J Am Acad Dermatol 74:1012-1014.
- Hertweck A et al. (2016) T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex. Cell Rep 15:2756-2770
- Hosokawa H et al. (2016) Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells. Nat Commun 7:11289.
- Szabo SJ et al. (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
- Yang R et al. (2020) Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria. Cell 183:1826-1847