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Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Immunity | 2017

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration.

Pubmed ID: 29166588 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

  • Agency: British Heart Foundation, United Kingdom
    Id: FS/12/38/29640
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BBS/E/B/000C0407
  • Agency: British Heart Foundation, United Kingdom
    Id: PG/15/105/31906
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/14/2/30616
  • Agency: British Heart Foundation, United Kingdom
    Id: CH/15/2/32064
  • Agency: British Heart Foundation, United Kingdom
    Id: CH/15/2/32064
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BBS/E/B/000C0409
  • Agency: British Heart Foundation, United Kingdom
    Id: FS/11/64/28945

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Addgene (tool)

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laboratory mouse with name BALB/cAnNCrl from MGI.

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CBA/Ca (tool)

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laboratory mouse with name CBA/Ca from MGI.

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Hexokinase 1 antibody (antibody)

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Hexokinase 1 antibody (antibody)

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This polyclonal targets Hexokinase 1 antibody

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Hexokinase II antibody (antibody)

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RRID:AB_2315148

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GLK antibody (antibody)

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RRID:AB_97863

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