期刊
CLINICAL IMMUNOLOGY
卷 131, 期 3, 页码 385-394出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2009.02.009
关键词
T-bet; EGR1; Promoter; Transcription; T helper cells; TCR signaling
类别
资金
- Korea Science and Engineering Foundation through the Rheumatism Research Center [RII-2002-098-05003]
- Ministry of Health and Welfare [03-PJ10-PG13-GD01-0002]
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. (C) 2009 Elsevier Inc. All rights reserved.
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