Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Line
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Gene Expression Regulation*
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Humans
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukins / genetics
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Interleukins / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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NFATC Transcription Factors
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology*
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Promoter Regions, Genetic
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Sequence Alignment
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T-Box Domain Proteins
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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Transcription Factors / genetics
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Transcription Factors / immunology*
Substances
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DNA-Binding Proteins
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Interleukins
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NFATC Transcription Factors
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NFATC2 protein, human
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Nfatc2 protein, mouse
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Nuclear Proteins
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transcription Factors
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Interferon-gamma
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interleukin-21