NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression
NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression
复制标题
DOI：
10.1073/pnas.0409512102
复制
发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Grusby, MJ
中科院分区：
文献类型：
--
作者：
Mehta, DS;Wurster, AL;Grusby, MJ
除了经典的Th2细胞因子IL-4、IL-5和IL-13外，辅助性T细胞(Th)2细胞还选择性地表达IL-21。与这些聚集的Th2细胞细胞因子基因不同，IL-21基因位于不同的染色体上，并且不受指导其他Th2细胞因子表达的相同位点控制区的协调调节。我们证明IL-21的近端启动子通过NFATc2和T-bet的作用来控制其Th细胞亚群的特异性表达。NFATc2直接结合并激活Th2细胞中IL-21启动子的转录，而T-bet通过抑制NFATc2与Th1细胞中IL-21启动子的结合来抑制IL-21转录。这些数据表明，Th细胞亚群特异性细胞因子基因的调控机制有多种。
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.