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dc.contributor.authorAlmeida, Luís
dc.contributor.authorDhillon-LaBrooy, Ayesha
dc.contributor.authorCastro, Carla N
dc.contributor.authorAdossa, Nigatu
dc.contributor.authorCarriche, Guilhermina M
dc.contributor.authorGuderian, Melanie
dc.contributor.authorLippens, Saskia
dc.contributor.authorDennerlein, Sven
dc.contributor.authorHesse, Christina
dc.contributor.authorLambrecht, Bart N
dc.contributor.authorBerod, Luciana
dc.contributor.authorSchauser, Leif
dc.contributor.authorBlazar, Bruce R
dc.contributor.authorKalesse, Markus
dc.contributor.authorMüller, Rolf
dc.contributor.authorMoita, Luís F
dc.contributor.authorSparwasser, Tim
dc.date.accessioned2021-01-29T15:54:04Z
dc.date.available2021-01-29T15:54:04Z
dc.date.issued2020-11-24
dc.identifier.citationImmunity. 2021 Jan 12;54(1):68-83.e6. doi: 10.1016/j.immuni.2020.11.001. Epub 2020 Nov 24.en_US
dc.identifier.pmid33238133
dc.identifier.doi10.1016/j.immuni.2020.11.001
dc.identifier.urihttp://hdl.handle.net/10033/622709
dc.description.abstractWhile antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.en_US
dc.language.isoenen_US
dc.publisherElsevier (Cell Press)en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectArgyrinen_US
dc.subjectLinezoliden_US
dc.subjectNAD+en_US
dc.subjectT cellsen_US
dc.subjectantibioticsen_US
dc.subjectautoimmunityen_US
dc.subjectelongation factor G1en_US
dc.subjectmitochondriaen_US
dc.subjectmitochondrial translationen_US
dc.subjectribosome-targetingen_US
dc.titleRibosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis.en_US
dc.typeArticleen_US
dc.identifier.eissn1097-4180
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.;HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalImmunityen_US
dc.source.volume54
dc.source.issue1
dc.source.beginpage68
dc.source.endpage83.e6
refterms.dateFOA2021-01-29T15:54:05Z
dc.source.journaltitleImmunity
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International