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dc.contributor.authorBalmer, Maria L
dc.contributor.authorMa, Eric H
dc.contributor.authorThompson, Andrew
dc.contributor.authorEpple, Raja
dc.contributor.authorUnterstab, Gunhild
dc.contributor.authorLötscher, Jonas
dc.contributor.authorDehio, Philippe
dc.contributor.authorSchürch, Christian M
dc.contributor.authorWarncke, Jan D
dc.contributor.authorPerrin, Gaëlle
dc.contributor.authorWoischnig, Anne-Kathrin
dc.contributor.authorGrählert, Jasmin
dc.contributor.authorLöliger, Jordan
dc.contributor.authorAssmann, Nadine
dc.contributor.authorBantug, Glenn R
dc.contributor.authorSchären, Olivier P
dc.contributor.authorKhanna, Nina
dc.contributor.authorEgli, Adrian
dc.contributor.authorBubendorf, Lukas
dc.contributor.authorRentsch, Katharina
dc.contributor.authorHapfelmeier, Siegfried
dc.contributor.authorJones, Russell G
dc.contributor.authorHess, Christoph
dc.date.accessioned2020-07-17T23:30:32Z
dc.date.available2020-07-17T23:30:32Z
dc.date.issued2020-09-01
dc.identifier.issn1550-4131
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/308104
dc.description.abstractSerum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleMemory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.
dc.typeArticle
prism.endingPage467.e5
prism.issueIdentifier3
prism.publicationDate2020
prism.publicationNameCell Metab
prism.startingPage457
prism.volume32
dc.identifier.doi10.17863/CAM.55198
dcterms.dateAccepted2020-07-12
rioxxterms.versionofrecord10.1016/j.cmet.2020.07.004
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-09
dc.contributor.orcidThompson, Andrew [0000-0002-7046-6792]
dc.identifier.eissn1932-7420
rioxxterms.typeJournal Article/Review
cam.orpheus.successWed Aug 19 08:05:30 BST 2020 - Embargo updated
cam.orpheus.counter4
rioxxterms.freetoread.startdate2021-07-31


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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