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
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View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionslaboratory mouse with name CBA/Ca from MGI.
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View all literature mentionsThis monoclonal targets CD45RA
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View all literature mentionsThis monoclonal targets CD357 (AITR/GITR)
View all literature mentionsThis monoclonal targets CD127
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View all literature mentionsThis unknown targets IgG
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View all literature mentionsThis monoclonal targets CD28
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View all literature mentionsThis monoclonal targets CD25
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View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis monoclonal targets CD357 (AITR/GITR)
View all literature mentionsThis monoclonal targets CD127
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets Hk2
View all literature mentionsThis unknown targets Rabbit IgG
View all literature mentionsThis unknown targets IgG
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View all literature mentionsThis unknown targets IgG Fc fragment
View all literature mentionsThis unknown targets Negative Control ARMENIAN HAMSTER IgG NEGATIVE CONTROL
View all literature mentionsThis polyclonal targets Hamster IgG
View all literature mentionsThis monoclonal targets HAMSTER ANTI MOUSE CD28
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD8a
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View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis polyclonal targets ALDOB
View all literature mentionsThis polyclonal targets Enolase-1
View all literature mentionsThis monoclonal targets LPAM-1
View all literature mentionsThis monoclonal targets CD197
View all literature mentionsThis monoclonal targets CD194
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets CD54
View all literature mentionsThis monoclonal targets CD49d
View all literature mentionsThis monoclonal targets CD40
View all literature mentionsThis monoclonal targets CD31 (PECAM-1)
View all literature mentionsThis monoclonal targets CD29
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View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD11a (LFA-1alpha)
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD3
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