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    Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2016-21. Epub 2005 Jan 31.

    NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression.

    Mehta DS, Wurster AL, Weinmann AS, Grusby MJ.

    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

    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.

    PMID: 15684054 [PubMed - indexed for MEDLINE]

    PMCID: PMC548571

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