NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression
DS Mehta, AL Wurster… - Proceedings of the …, 2005 - National Acad Sciences
DS Mehta, AL Wurster, AS Weinmann, MJ Grusby
Proceedings of the National Academy of Sciences, 2005•National Acad SciencesT 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 …
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 …
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.
National Acad Sciences