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    Home > Active Ingredient News > Immunology News > PNAS: IRF-4 regulates the effector function of CD8+ memory T cells

    PNAS: IRF-4 regulates the effector function of CD8+ memory T cells

    • Last Update: 2021-06-19
    • Source: Internet
    • Author: User
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    April 25, 2021 //---It is well known that the transcription factor IRF4 is necessary for CD8 + T cell activation, proliferation and differentiation into effector cells, so it is essential for CD8 + T cell response
    .
    However, the function of IRF4 in memory CD8 + T cells remains to be explored
    .
    In order to study the role of IRF4 in the maintenance of differentiation and the survival of CD8+ memory T cells, Friederike Raczkowski's team from the University of Hamburg, Germany used a mouse model of tamoxifen-induced Irf4 knockout, revealing that IRF4 has effects on CD8+ memory T The role of cells, related results were published in the recent "PNAS" magazine
    .




    (Image source:transcription factor IRF4 is necessary for the activation of CD8 + T cells and their differentiation into effector T cells
    .
    In the absence of IRF4, CD8+ T cell activation is impaired, and it may also affect the development and number of CD8+ memory T cells
    .
    In this regard, the authors used an inducible Irf4 gene deletion mouse model to rule out the inefficient differentiation of memory cells due to the lack of IRF4
    .
    Irf4 fl/fl mice are crossed with CreERT2 mice.
    In Irf4fl/fl mice, Cre-mediated gene recombination will result in the loss of exons I and II in the Irf4 gene and the constitutive expression of green fluorescent protein (GFP)
    .


    (Figure 1, Design and performance confirmation of inducible IRF-4 deletion mutant mice)

    Afterwards, the mice were infected with Ovalbumin recombinant Listeria, and after the pathogen was eliminated, Irf4 knockout was induced
    .
    The results showed that the loss of IRF4 caused the phenotypic changes of CD8+ memory T cells, but did not lead to a decrease in the total memory T cell population
    .
    However, after encountering the pathogen again, the expansion capacity and effect of CD8 + memory T cells were significantly impaired
    .
    Further studies have shown that compared with CD8+ effector memory T cells, CD8+ tissue-resident memory T cells (TRM cells) express higher levels of IRF4
    .
    Constitutive Irf4 knockout mice reduced the number of CD8 + TRM cells, while tamoxifen-induced Irf4 deletion resulted in a decrease in the number of cells
    .


    In summary, the findings indicate that IRF4 is required for effective activation, not for the general survival of CD8+ memory T cells
    .
    In contrast, the formation and maintenance of CD8 + TRM cells seems to depend on IRF4
    .
    (Bioon.
    com)

    Original source: Aenne Harberts, Constantin Schmidt, Joanna Schmid et al.
    , Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences Apr 2021, 118 (16) e2014553118; DOI: 10.
    1073/pnas.
    2014553118
    (Figure 1, Design and performance confirmation of inducible IRF-4 deletion mutant mice)

    Afterwards, the mice were infected with Ovalbumin recombinant Listeria, and after the pathogen was eliminated, Irf4 knockout was induced
    .
    The results showed that the loss of IRF4 caused the phenotypic changes of CD8+ memory T cells, but did not lead to a decrease in the total memory T cell population
    .
    However, after encountering the pathogen again, the expansion capacity and effect of CD8 + memory T cells were significantly impaired
    .
    Further studies have shown that compared with CD8+ effector memory T cells, CD8+ tissue-resident memory T cells (TRM cells) express higher levels of IRF4
    .
    Constitutive Irf4 knockout mice reduced the number of CD8 + TRM cells, while tamoxifen-induced Irf4 deletion resulted in a decrease in the number of cells
    .


    In summary, the findings indicate that IRF4 is required for effective activation, not for the general survival of CD8+ memory T cells
    .
    In contrast, the formation and maintenance of CD8 + TRM cells seems to depend on IRF4
    .
    (Bioon.
    com)

    Original source: Aenne Harberts, Constantin Schmidt, Joanna Schmid et al.
    , Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences Apr 2021, 118 (16) e2014553118; DOI: 10.
    1073/pnas.
    2014553118

    Afterwards, the mice were infected with Ovalbumin recombinant Listeria, and after the pathogen was eliminated, Irf4 knockout was induced
    .
    The results showed that the loss of IRF4 caused the phenotypic changes of CD8+ memory T cells, but did not lead to a decrease in the total memory T cell population
    .
    However, after encountering the pathogen again, the expansion capacity and effect of CD8 + memory T cells were significantly impaired
    .
    Further studies have shown that compared with CD8+ effector memory T cells, CD8+ tissue-resident memory T cells (TRM cells) express higher levels of IRF4
    .
    Constitutive Irf4 knockout mice reduced the number of CD8 + TRM cells, while tamoxifen-induced Irf4 deletion resulted in a decrease in the number of cells
    .


    In summary, the findings indicate that IRF4 is required for effective activation, not for the general survival of CD8+ memory T cells
    .
    In contrast, the formation and maintenance of CD8 + TRM cells seems to depend on IRF4
    .
    (Bioon.
    com)

    Original source: Aenne Harberts, Constantin Schmidt, Joanna Schmid et al.
    , Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences Apr 2021, 118 (16) e2014553118; DOI: 10.
    1073/pnas.
    2014553118


    In summary, the findings indicate that IRF4 is required for effective activation, not for the general survival of CD8+ memory T cells
    .
    In contrast, the formation and maintenance of CD8 + TRM cells seems to depend on IRF4
    .
    (Bioon.
    com)

    Original source: Aenne Harberts, Constantin Schmidt, Joanna Schmid et al.
    , Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences Apr 2021, 118 (16) e2014553118; DOI: 10.
    1073/pnas.
    2014553118


    Original source: Aenne Harberts, Constantin Schmidt, Joanna Schmid et al.
    , Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences Apr 2021, 118 (16) e2014553118; DOI: 10.
    1073/pnas.
    2014553118
    Original source: Interferon regulatory factor 4 controls effector functions of CD8+ memory T cells.
    Proceedings of the National Academy of Sciences
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