2024
A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation
Bonetti L, Horkova V, Grusdat M, Longworth J, Guerra L, Kurniawan H, Franchina D, Soriano-Baguet L, Binsfeld C, Verschueren C, Spath S, Ewen A, Koncina E, Gérardy J, Kobayashi T, Dostert C, Farinelle S, Härm J, Fan Y, Chen Y, Harris I, Lang P, Vasiliou V, Waisman A, Letellier E, Becher B, Mittelbronn M, Brenner D. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabolism 2024, 36: 1726-1744.e10. PMID: 38986617, DOI: 10.1016/j.cmet.2024.06.010.Peer-Reviewed Original ResearchReactive oxygen speciesMitochondrial functionCatalytic subunit of glutamate cysteine ligaseMitochondrial gene expressionDecreased cellular ATPPhosphorylation of 4E-BP1Disrupt mitochondrial functionReduced phosphorylation of 4E-BP1T cell-specific ablationCell's antioxidant mechanismsCell-specific ablationCatalytic subunitIL-22Cellular signalingIntestinal homeostasisIL-22 productionSignificant reactive oxygen speciesSubunit of glutamate cysteine ligaseGene expressionReduced IL-22 productionReduced phosphorylationCellular ATPGut protectionProtein synthesisGlutamate cysteine ligase
2021
m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity
Zhou J, Zhang X, Hu J, Qu R, Yu Z, Xu H, Chen H, Yan L, Ding C, Zou Q, Ye Y, Wang Z, Flavell RA, Li HB. m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity. Science Advances 2021, 7: eabg0470. PMID: 34134995, PMCID: PMC8208713, DOI: 10.1126/sciadv.abg0470.Peer-Reviewed Original ResearchAlkB homolog 5T cell-specific ablationT cellsMRNA stabilityCell-specific ablationMethyladenosine (m<sup>6</sup>A) modificationHomolog 5Pathogenicity of CD4Messenger RNAErasersProtein expressionAdoptive transfer colitisExperimental autoimmune encephalomyelitisHomeostasis of CD4T cell responsesSpecific roleT cell pathogenicityCentral nervous system
2017
Glutathione Primes T Cell Metabolism for Inflammation
Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation. Immunity 2017, 46: 675-689. PMID: 28423341, DOI: 10.1016/j.immuni.2017.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEncephalomyelitis, Autoimmune, ExperimentalEnergy MetabolismGlutamate-Cysteine LigaseGlutamineGlutathioneGlycolysisImmunoblottingInflammationMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsProto-Oncogene Proteins c-mycReactive Oxygen SpeciesSignal TransductionT-LymphocytesTOR Serine-Threonine KinasesConceptsReactive oxygen speciesMYC transcription factorsConditional gene targetingT cell-specific ablationGlutamate-cysteine ligaseT cell metabolismRapamycin 1Catalytic subunitMetabolic integrationTranscription factorsGene targetingMetabolic reprogrammingBiosynthetic requirementsUnexpected roleExpression of NFATAntiviral defenseCysteine ligaseCell metabolismGSH pathwayMammalian targetGSH productionMurine TGSH deficiencyOxygen speciesCell effector functions
2014
Signaling through the Adaptor Molecule MyD88 in CD4+ T Cells Is Required to Overcome Suppression by Regulatory T Cells
Schenten D, Nish SA, Yu S, Yan X, Lee HK, Brodsky I, Pasman L, Yordy B, Wunderlich FT, Brüning JC, Zhao H, Medzhitov R. Signaling through the Adaptor Molecule MyD88 in CD4+ T Cells Is Required to Overcome Suppression by Regulatory T Cells. Immunity 2014, 40: 78-90. PMID: 24439266, PMCID: PMC4445716, DOI: 10.1016/j.immuni.2013.10.023.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCells, CulturedImmunity, InnateImmunologic MemoryImmunosuppression TherapyInterleukin-1Interleukin-18MiceMice, Inbred C57BLMice, TransgenicMyeloid Differentiation Factor 88Organ SpecificityReceptors, Interleukin-1Signal TransductionT-Lymphocytes, RegulatoryTh1 CellsTh17 CellsConceptsToll-like receptorsTh1 cell responsesT cellsCell-specific ablationCell responsesIL-1Interleukin-1 receptor family memberT helper 17 (Th17) cell responsesTreg cell-mediated suppressionTreg cell-specific ablationT cell-specific ablationRegulatory T cellsT regulatory (Treg) cellsCell-mediated suppressionMemory T cellsAdaptor molecule MyD88Adaptive immune responsesIL-1 actsTreg cellsRegulatory cellsReceptor family membersMolecule MyD88Th1 cellsImmune responseMyD88
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