Involvement of GATA3 in Protein Kinase C θ‐induced Th2 cytokine expression

Protein kinase C θ (PKCθ) is essential for T cell activation, as it is required for the activation of NF‐κB and expression of IL‐2. PKCθ has also been shown to affect NFAT activation and Th2 differentiation. To better understand the role of PKCθ in the regulation of T helper cells, we used PKCθ‐defi...

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Bibliographic Details
Published in:European journal of immunology 2006-12, Vol.36 (12), p.3305-3314
Main Authors: Stevens, Lisa, Htut, Tin M., White, Della, Li, Xiang, Hanidu, Adedayo, Stearns, Carol, Labadia, Mark E., Li, Jun, Brown, Maryanne, Yang, Jianfei
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cytokines
Cytokines - biosynthesis
Cytokines - genetics
GATA3 Transcription Factor - biosynthesis
GATA3 Transcription Factor - genetics
GATA3 Transcription Factor - physiology
Gene regulation
Interferon-gamma - biosynthesis
Interferon-gamma - genetics
Isoenzymes - physiology
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Protein Kinase C - physiology
Protein Kinase C-theta
Protein kinases/phosphatases
Th1/Th2 cells
Th2 Cells - enzymology
Th2 Cells - immunology
Th2 Cells - metabolism
Transcription factors
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
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Summary:Protein kinase C θ (PKCθ) is essential for T cell activation, as it is required for the activation of NF‐κB and expression of IL‐2. PKCθ has also been shown to affect NFAT activation and Th2 differentiation. To better understand the role of PKCθ in the regulation of T helper cells, we used PKCθ‐deficient DO11.10 transgenic T cells to study its role in vitro. DO11.10 Th1 cells deficient in PKCθ produced significantly less TNF‐α and IL‐2. The expression of Th2 cytokines, including IL‐4, IL‐5, IL‐10, IL‐13 and IL‐24 was significantly reduced in PKCθ‐deficient T cells. Moreover, the expression of the Th2 transcription factor, GATA3, was significantly reduced in PKCθ‐deficient T cells. Overexpression of GATA3 by retroviral infection in PKCθ‐deficient T cells resulted in increased expansion of IL‐4‐producing T cells and higher IL‐4 production than that of wild type Th2 cells. IL‐5, IL‐10, IL‐13 and IL‐24 expressions were also rescued by GATA3 overexpression. Our observations suggest that PKCθ regulates Th2 cytokine expression via GATA3.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200636400