T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells
Autor: | R Q, Cron, S J, Bort, Y, Wang, M W, Brunvand, D B, Lewis |
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Rok vydání: | 1999 |
Předmět: |
Adult
CD4-Positive T-Lymphocytes Cell Nucleus NFATC Transcription Factors Transcription Genetic Molecular Sequence Data Nuclear Proteins Lymphocyte Activation DNA-Binding Proteins Gene Expression Regulation Humans Amino Acid Sequence Interleukin-4 5' Untranslated Regions Promoter Regions Genetic Interphase Transcription Factors |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(2) |
ISSN: | 0022-1767 |
Popis: | The repetitive activation of T cells (priming) enhances the expression of many cytokines, such as IL-4, but not others, such as IL-2. Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood. Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells (NFAT) proteins. As detected by in vivo footprinting, priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter. Moreover, each proximal P element is essential for optimal IL-4 promoter activity. Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells, while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar. Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells, suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type. Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells. NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells. |
Databáze: | OpenAIRE |
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