LKB1 Mediates the Development of Conventional and Innate T Cells via AMP-Dependent Kinase Autonomous Pathways

Marouan Zarrouk, Julia Rolf, Doreen Ann Cantrell

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature alpha/beta T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant V alpha 14 NKT cells and innate TCR alpha beta gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase ( AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.

    Original languageEnglish
    Article numbere60217
    Number of pages9
    JournalPLoS ONE
    Volume8
    Issue number3
    DOIs
    Publication statusPublished - 22 Mar 2013

    Keywords

    • ACTIVATION
    • C-MYC
    • PRECURSORS
    • THYMUS
    • INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

    Cite this

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    title = "LKB1 Mediates the Development of Conventional and Innate T Cells via AMP-Dependent Kinase Autonomous Pathways",
    abstract = "The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature alpha/beta T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant V alpha 14 NKT cells and innate TCR alpha beta gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase ( AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.",
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    author = "Marouan Zarrouk and Julia Rolf and Cantrell, {Doreen Ann}",
    year = "2013",
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    doi = "10.1371/journal.pone.0060217",
    language = "English",
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    LKB1 Mediates the Development of Conventional and Innate T Cells via AMP-Dependent Kinase Autonomous Pathways. / Zarrouk, Marouan; Rolf, Julia; Cantrell, Doreen Ann.

    In: PLoS ONE, Vol. 8, No. 3, e60217, 22.03.2013.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - LKB1 Mediates the Development of Conventional and Innate T Cells via AMP-Dependent Kinase Autonomous Pathways

    AU - Zarrouk, Marouan

    AU - Rolf, Julia

    AU - Cantrell, Doreen Ann

    PY - 2013/3/22

    Y1 - 2013/3/22

    N2 - The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature alpha/beta T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant V alpha 14 NKT cells and innate TCR alpha beta gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase ( AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.

    AB - The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature alpha/beta T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant V alpha 14 NKT cells and innate TCR alpha beta gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase ( AMPK). The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.

    KW - ACTIVATION

    KW - C-MYC

    KW - PRECURSORS

    KW - THYMUS

    KW - INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

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    DO - 10.1371/journal.pone.0060217

    M3 - Article

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    JO - PLoS ONE

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