Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking

Linda V. Sinclair, David Finlay, Carmen Feijoo, Georgina H. Cornish, Alex Gray, Ann Ager, Klaus Okkenhaug, Thijs J. Hagenbeek, Hergen Spits, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    290 Citations (Scopus)

    Abstract

    Phosphatidylinositol-3-OH kinase (PI(3) K) and the nutrient sensor mTOR are evolutionarily conserved regulators of cell metabolism. Here we show that PI(3) K and mTOR determined the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. The key lymph node-homing receptors CD62L (L-selectin) and CCR7 were highly expressed on naive T lymphocytes but were downregulated after immune activation. CD62L downregulation occurred through ectodomain proteolysis and suppression of gene transcription. The p110 delta subunit of PI(3) K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110d was mediated by mTOR through regulation of the transcription factor KLF2. PI(3) K-mTOR nutrient-sensing pathways also determined expression of the chemokine receptor CCR7 and regulated lymphocyte trafficking in vivo. Hence, lymphocytes use PI(3) K and mTOR to match metabolism and trafficking.

    Original languageEnglish
    Pages (from-to)513-521
    Number of pages9
    JournalNature Immunology
    Volume9
    Issue number5
    DOIs
    Publication statusPublished - May 2008

    Keywords

    • Animals
    • Cell Movement
    • L-Selectin
    • Lymph Nodes
    • Lymphocyte Activation
    • Mice
    • Mice, Inbred C57BL
    • Mice, Transgenic
    • Phosphatidylinositol 3-Kinases
    • Protein Kinases
    • Receptors, CCR7
    • Signal Transduction
    • T-Lymphocytes
    • TOR Serine-Threonine Kinases

    Research Output

    • 290 Citations
    • 1 Comment/debate

    Corrigendum: Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking (Nature Immunology (2008) vol. 9(6) (513-521))

    Sinclair, L. V., Finlay, D., Feijoo, C., Cornish, G. H., Gray, A., Ager, A., Okkenhaug, K., Hagenbeek, T. J., Spits, H. & Cantrell, D. A., Jun 2008, In : Nature Immunology. 9, 6, p. 692 1 p.

    Research output: Contribution to journalComment/debate

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