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...
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 131(2009), 3 vom: 15. Juni, Seite 385-94 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2009
|
Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | 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 |
Zusammenfassung: | 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 |
---|---|
Beschreibung: | 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 |