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dc.contributor.authorKishore, Madhav
dc.contributor.authorCheung, Kenneth CP
dc.contributor.authorFu, Hongmei
dc.contributor.authorBonacina, Fabrizia
dc.contributor.authorWang, Guosu
dc.contributor.authorCoe, David
dc.contributor.authorWard, Eleanor J
dc.contributor.authorColamatteo, Alessandra
dc.contributor.authorJangani, Maryam
dc.contributor.authorBaragetti, Andrea
dc.contributor.authorMatarese, Giuseppe
dc.contributor.authorSmith, David M
dc.contributor.authorHaas, Robert
dc.contributor.authorMauro, Claudio
dc.contributor.authorWraith, David C
dc.contributor.authorOkkenhaug, Klaus
dc.contributor.authorCatapano, Alberico L
dc.contributor.authorDe Rosa, Veronica
dc.contributor.authorNorata, Giuseppe D
dc.contributor.authorMarelli-Berg, Federica M
dc.date.accessioned2018-01-24T09:29:15Z
dc.date.available2018-01-24T09:29:15Z
dc.date.issued2017-11-21
dc.identifier.issn1074-7613
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/271041
dc.description.abstractMigration 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.
dc.format.mediumPrint
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCells, Cultured
dc.subjectAnimals
dc.subjectMice, Inbred Strains
dc.subjectHumans
dc.subjectMice
dc.subjectGlucokinase
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectGlycolysis
dc.subjectT-Lymphocytes, Regulatory
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectCTLA-4 Antigen
dc.subjectMechanistic Target of Rapamycin Complex 1
dc.subjectMechanistic Target of Rapamycin Complex 2
dc.subjectCD28 Antigens
dc.titleRegulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.
dc.typeArticle
prism.endingPage889.e10
prism.issueIdentifier5
prism.publicationDate2017
prism.publicationNameImmunity
prism.startingPage875
prism.volume47
dc.identifier.doi10.17863/CAM.18003
dcterms.dateAccepted2017-10-26
rioxxterms.versionofrecord10.1016/j.immuni.2017.10.017
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-11
dc.contributor.orcidOkkenhaug, Klaus [0000-0002-9432-4051]
dc.identifier.eissn1097-4180
rioxxterms.typeJournal Article/Review


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International