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

doi:https://doi.org/10.1038/ni.1603

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

Research output: Contribution to journal › Article › Academic › peer-review

328 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 p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta 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 language	English
Pages (from-to)	513-521
Journal	Nature immunology
Volume	9
Issue number	5
DOIs	https://doi.org/10.1038/ni.1603
Publication status	Published - 2008

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https://doi.org/10.1038/ni.1603

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title = "Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking",

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 p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta 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",

author = "Sinclair, {Linda V.} and David Finlay and Carmen Feijoo and Cornish, {Georgina H.} and Alex Gray and Ann Ager and Klaus Okkenhaug and Hagenbeek, {Thijs J.} and Hergen Spits and Cantrell, {Doreen A.}",

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T1 - Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking

AU - Sinclair, Linda V.

AU - Finlay, David

AU - Feijoo, Carmen

AU - Cornish, Georgina H.

AU - Gray, Alex

AU - Ager, Ann

AU - Okkenhaug, Klaus

AU - Hagenbeek, Thijs J.

AU - Spits, Hergen

AU - Cantrell, Doreen A.

PY - 2008

Y1 - 2008

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AB - 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 p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta 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

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