T-bet expression is regulated by EGR1-mediated signaling in activated T cells
T-bet is a Th1-specific transcription factor that is directly involved in three important pathways for Th1 cell differentiation, namely TCR signaling, and the IFN-gamma-STAT1 and IL-12-STAT4 pathways. A recent study also showed that T-bet plays a vital role in innate immunity. However, the molecular...
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 131(2009), 3 vom: 15. Juni, Seite 385-94 |
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| Auteur principal: | |
| Autres auteurs: | , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2009
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't EGR1 protein, human Early Growth Response Protein 1 Receptors, Antigen, T-Cell T-Box Domain Proteins T-bet Transcription Factor |
| Résumé: | T-bet is a Th1-specific transcription factor that is directly involved in three important pathways for Th1 cell differentiation, namely TCR signaling, and the IFN-gamma-STAT1 and IL-12-STAT4 pathways. A recent study also showed that T-bet plays a vital role in innate immunity. However, the molecular mechanism responsible for transcriptional activation of T-bet during T cell development is not yet known. Here, we characterize the essential human T-bet promoter elements and show that binding of EGR1 to this promoter induces T-bet transcription. Notably, overexpression of EGR1 transactivates and, synergistically in concert with TCR signaling, induces T-bet expression in activated T cells. In contrast, depletion of EGR1 significantly decreases T-bet induction. Finally, we report a positive correlation between EGR1 and T-bet expression during T helper cell differentiation. Collectively, these findings provide molecular insight into T-bet transcription and suggest that EGR1 is an upstream regulator of T-bet induction |
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| Description: | Date Completed 09.06.2009 Date Revised 03.01.2025 published: Print Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2009.02.009 |