The impact of KLF2 modulation on the transcriptional program and function of CD8 T Cells

Gavin C. Preston, Carmen Feijoo-Carnero, Nick Schurch, Victoria H. Cowling, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Krüppel-like factor 2 (KLF2) is a transcription factor that is highly expressed in quiescent T lymphocytes and downregulated in effector T cells. We now show that antigen receptor engagement downregulates KLF2 expression in a graded response determined by the affinity of T cell antigen receptor (TCR) ligand and the integrated activation of protein kinase B and the MAP kinases ERK1/2. The present study explores the importance of KLF2 downregulation and reveals that the loss of KLF2 controls a select portion of the CD8 effector T cell transcriptional program. In particular, KLF2 loss is required for CD8 T cells to express the inflammatory chemokine receptor CXCR3 and for maximum clonal expansion of T cells. KLF2 thus negatively controls the ability of CD8 T cells to respond to the CXCR3 ligand CXCL10. Strikingly, the KLF2 threshold for restraining expression of CXCR3 is very low and quite distinct to the KLF2 threshold for restraining T cell proliferation. KLF2 is thus an analogue (tunable) not a digital (on/off) cellular switch where the magnitude of KLF2 expression differentially modifies the T cell responses.
    Original languageEnglish
    Article numbere77537
    Number of pages16
    JournalPLoS ONE
    Volume8
    Issue number10
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    T-cells
    T-lymphocytes
    Modulation
    T-Lymphocytes
    Down-Regulation
    Ligands
    Proto-Oncogene Proteins c-akt
    Antigen Receptors
    antigens
    Mitogen-Activated Protein Kinase 3
    portion size
    Chemokine Receptors
    Mitogen-Activated Protein Kinase 1
    Mitogen-Activated Protein Kinase Kinases
    Cell proliferation
    receptors
    T-Cell Antigen Receptor
    Protein Kinases
    mitogen-activated protein kinase
    protein kinases

    Cite this

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    title = "The impact of KLF2 modulation on the transcriptional program and function of CD8 T Cells",
    abstract = "Kr{\"u}ppel-like factor 2 (KLF2) is a transcription factor that is highly expressed in quiescent T lymphocytes and downregulated in effector T cells. We now show that antigen receptor engagement downregulates KLF2 expression in a graded response determined by the affinity of T cell antigen receptor (TCR) ligand and the integrated activation of protein kinase B and the MAP kinases ERK1/2. The present study explores the importance of KLF2 downregulation and reveals that the loss of KLF2 controls a select portion of the CD8 effector T cell transcriptional program. In particular, KLF2 loss is required for CD8 T cells to express the inflammatory chemokine receptor CXCR3 and for maximum clonal expansion of T cells. KLF2 thus negatively controls the ability of CD8 T cells to respond to the CXCR3 ligand CXCL10. Strikingly, the KLF2 threshold for restraining expression of CXCR3 is very low and quite distinct to the KLF2 threshold for restraining T cell proliferation. KLF2 is thus an analogue (tunable) not a digital (on/off) cellular switch where the magnitude of KLF2 expression differentially modifies the T cell responses.",
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    The impact of KLF2 modulation on the transcriptional program and function of CD8 T Cells. / Preston, Gavin C.; Feijoo-Carnero, Carmen; Schurch, Nick; Cowling, Victoria H.; Cantrell, Doreen A. (Lead / Corresponding author).

    In: PLoS ONE, Vol. 8, No. 10, e77537, 2013.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The impact of KLF2 modulation on the transcriptional program and function of CD8 T Cells

    AU - Preston, Gavin C.

    AU - Feijoo-Carnero, Carmen

    AU - Schurch, Nick

    AU - Cowling, Victoria H.

    AU - Cantrell, Doreen A.

    PY - 2013

    Y1 - 2013

    N2 - Krüppel-like factor 2 (KLF2) is a transcription factor that is highly expressed in quiescent T lymphocytes and downregulated in effector T cells. We now show that antigen receptor engagement downregulates KLF2 expression in a graded response determined by the affinity of T cell antigen receptor (TCR) ligand and the integrated activation of protein kinase B and the MAP kinases ERK1/2. The present study explores the importance of KLF2 downregulation and reveals that the loss of KLF2 controls a select portion of the CD8 effector T cell transcriptional program. In particular, KLF2 loss is required for CD8 T cells to express the inflammatory chemokine receptor CXCR3 and for maximum clonal expansion of T cells. KLF2 thus negatively controls the ability of CD8 T cells to respond to the CXCR3 ligand CXCL10. Strikingly, the KLF2 threshold for restraining expression of CXCR3 is very low and quite distinct to the KLF2 threshold for restraining T cell proliferation. KLF2 is thus an analogue (tunable) not a digital (on/off) cellular switch where the magnitude of KLF2 expression differentially modifies the T cell responses.

    AB - Krüppel-like factor 2 (KLF2) is a transcription factor that is highly expressed in quiescent T lymphocytes and downregulated in effector T cells. We now show that antigen receptor engagement downregulates KLF2 expression in a graded response determined by the affinity of T cell antigen receptor (TCR) ligand and the integrated activation of protein kinase B and the MAP kinases ERK1/2. The present study explores the importance of KLF2 downregulation and reveals that the loss of KLF2 controls a select portion of the CD8 effector T cell transcriptional program. In particular, KLF2 loss is required for CD8 T cells to express the inflammatory chemokine receptor CXCR3 and for maximum clonal expansion of T cells. KLF2 thus negatively controls the ability of CD8 T cells to respond to the CXCR3 ligand CXCL10. Strikingly, the KLF2 threshold for restraining expression of CXCR3 is very low and quite distinct to the KLF2 threshold for restraining T cell proliferation. KLF2 is thus an analogue (tunable) not a digital (on/off) cellular switch where the magnitude of KLF2 expression differentially modifies the T cell responses.

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