期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 6, 页码 2016-2021出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409512102
关键词
cytokine; promoter; transcription factor
资金
- NIAID NIH HHS [R01 AI040171, AI061061, R56 AI061061, AI40171, AI056296, R01 AI061061, P01 AI056296] Funding Source: Medline
- NIGMS NIH HHS [GM 62135, R01 GM062135] Funding Source: Medline
T helper (Th) 2 cells selectively express IL-21 in addition to the classic Th2 cytokines IL-4, IL-5, and IL-13. In contrast to these clustered Th2 cell cytokine genes, the IL-21 gene resides on a different chromosome and is not coordinately regulated by the same locus control region that directs the expression of other Th2 cytokines. We demonstrate that the proximal promoter of IL-21 controls its Th-cell-subset-specific expression through the action of NFATc2 and T-bet. Whereas NFATc2 directly binds to and activates transcription of the IL-21 promoter in Th2 cells, T-bet represses IL-21 transcription by inhibiting the binding of NFATc2 to the promoter in Th1 cells. These data suggest that there are multiple mechanisms by which Th-cell-subset-specific cytokine genes are regulated.
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