2025
Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism
Steiner K, Young A, Patterson A, Sugiura A, Watson M, Preston S, Zhelonkin A, Jennings E, Chi C, Heintzman D, Pahnke A, Toudji Y, Hatem Z, Madden M, Arner E, Sewell A, Blount A, Okparaugo R, Fallman E, Krystofiak E, Sheldon R, Gibson-Corley K, Voss K, Nowinski S, Jones R, Mogilenko D, Rathmell J. Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism. The Journal Of Immunology 2025, 214: 958-976. PMID: 40204636, PMCID: PMC12123211, DOI: 10.1093/jimmun/vkaf034.Peer-Reviewed Original ResearchConceptsT cell subsetsCD4+ T cell subsetsMitochondrial fatty acid synthesisT cell functionT cellsFatty acid synthesisDecreased mitochondrial respirationTricarboxylic acid intermediatesLipid metabolism genesT cell fateSensitivity to ferroptosisIncreased cell deathCD4+ T cell functionCD8+ T cell numbersCD4+ T cell proliferationMitochondrial stressMetabolic genesCD4+ T cellsCRISPR/Cas9 screenMitochondrial respirationModel of inflammatory bowel diseaseAcid synthesisFitness disadvantageMemory T cellsT cell numbersNutrient-driven histone code determines exhausted CD8+ T cell fates
Ma S, Dahabieh M, Mann T, Zhao S, McDonald B, Song W, Chung H, Farsakoglu Y, Garcia-Rivera L, Hoffmann F, Xu S, Du V, Chen D, Furgiuele J, LaPorta M, Jacobs E, DeCamp L, Oswald B, Sheldon R, Ellis A, Liu L, He P, Wang Y, Jang C, Jones R, Kaech S. Nutrient-driven histone code determines exhausted CD8+ T cell fates. Science 2025, 387: eadj3020. PMID: 39666821, PMCID: PMC11881194, DOI: 10.1126/science.adj3020.Peer-Reviewed Original ResearchATP-citrate lyaseAcetyl-CoA synthetase 2Histone codeCD8<sup>+</sup> T cell differentiationTumor-specific T-cell responsesACLY inhibitionHistone acetylationCD8+ T cell fateExhausted T cellsT-cell therapyChronic viral infectionsT cell responsesT cell differentiationT cell fateT cell genesTex cellsT cellsEpigenetic modificationsEpigenetic remodelingViral infectionCitrate metabolismNutrient metabolismHistoneAcetylationDifferentiation
2024
Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation
Karginov T, Ménoret A, Leclair N, Harrison A, Chandiran K, Suarez-Ramirez J, Yurieva M, Karlinsey K, Wang P, O'Neill R, Murphy P, Adler A, Cauley L, Anczuków O, Zhou B, Vella A. Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation. Science 2024, 385: eadj1979. PMID: 39265028, PMCID: PMC11697694, DOI: 10.1126/science.adj1979.Peer-Reviewed Original ResearchConceptsRNA-binding proteinsT cell fateT cell receptor sensitivityT cell receptorPoison exonGenomes of jawed vertebratesPosttranscriptional regulatory mechanismsResponse to antigen receptor stimulationAntigen receptor stimulationTranscriptional regulationJawed vertebratesAlternative splicingSignaling transcriptsT cell survivalRegulatory mechanismsTCR sensitivitySplicingT-cell receptor gene rearrangementEffector T cell expansionT cell responses to antigenTRA2BT cell expansionResponse to antigenGene rearrangementsHistocompatibility complex
2021
The Complex Integration of T-cell Metabolism and Immunotherapy
Madden M, Rathmell J. The Complex Integration of T-cell Metabolism and Immunotherapy. Cancer Discovery 2021, 11: 1636-1643. PMID: 33795235, PMCID: PMC8295173, DOI: 10.1158/2159-8290.cd-20-0569.Peer-Reviewed Original ResearchConceptsT cell metabolismT cell functionT cellsImmune-oncology approachesEffector T cellsOxidative metabolismAdoptive cell therapyT cell interactionsT cell fateAntitumor immunityCancer immunotherapyImmune oncologyTumor microenvironmentNormal stimulationCell therapyTumorsAerobic glycolysisMetabolic reprogrammingMetabolic reprogramming eventsImmunotherapyMetabolismCellsTherapyCancerCentral role
2019
Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate
Tatsumi N, Iwasaki A, Kumamoto Y. Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate. The Journal Of Immunology 2019, 202: 56.9-56.9. DOI: 10.4049/jimmunol.202.supp.56.9.Peer-Reviewed Original ResearchCD4 T cellsOT-II cellsAntigen-specific CD4 T cellsDermal dendritic cellsDendritic cellsMHC class IIT cellsTh2 differentiationAntigen presentationCognate interactionPolyclonal CD4T cellsT cells 7 daysEffector CD4 T cellsT helper type 2 cellsMajor DC subsetsIL-4 productionEpidermal Langerhans cellsCells 7 daysType 2 cellsDC subsetsT cell fateLymph nodesOverall cell cycle progressionLangerhans cellsTh2 cells
2018
Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation
Lian G, Gnanaprakasam JR, Wang T, Wu R, Chen X, Liu L, Shen Y, Yang M, Yang J, Chen Y, Vasiliou V, Cassel TA, Green DR, Liu Y, Fan TW, Wang R. Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. ELife 2018, 7: e36158. PMID: 30198844, PMCID: PMC6152796, DOI: 10.7554/elife.36158.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationDimethyl FumarateGlutamate-Cysteine LigaseGlutamineGlutathioneGlutathione DisulfideHomeostasisLymphocyte ActivationMice, Inbred C57BLOxidation-ReductionOxidative StressReactive Oxygen SpeciesReceptors, Antigen, T-CellT-LymphocytesT-Lymphocytes, RegulatoryTh17 CellsConceptsCell fateDe novo synthesisNovo synthesisCell differentiationT cell differentiationMurine T cell differentiationT cell fateGlutamate-cysteine ligaseLineage choiceRedox demandsGlutathione de novo synthesisRecycling pathwayInhibition of GSHRedox homeostasisGSH biosynthesisGlutamine catabolismRedox balanceModifier subunitEssential precursorIntracellular GSHEssential roleGlutathione disulfideDifferentiationGSH contentGSHZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates
Guan T, Dominguez CX, Amezquita RA, Laidlaw BJ, Cheng J, Henao-Mejia J, Williams A, Flavell RA, Lu J, Kaech SM. ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates. Journal Of Experimental Medicine 2018, 215: 1153-1168. PMID: 29449309, PMCID: PMC5881466, DOI: 10.1084/jem.20171352.Peer-Reviewed Original ResearchConceptsT cellsMemory CD8T cell fateMemory T cell survivalLong-term immunityT cell formationT cell survivalMiR-200 family membersGrowth factor βFamily membersTranscription factor ZEB1Effector CD8MiR-200 familyCD8Mesenchymal transitionReciprocal expression patternCell fateZEB1ZEB2Factor βCell survivalTGFCell formationUnknown genetic pathwaysCell fate decisions
2007
Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor
Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SM. Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor. Immunity 2007, 27: 281-295. PMID: 17723218, PMCID: PMC2034442, DOI: 10.1016/j.immuni.2007.07.010.Peer-Reviewed Original ResearchConceptsMemory precursor effector cellsEffector cellsT cellsIL-15Higher T-bet expressionT-bet transcription factorT cell primingT-bet expressionAmount of inflammationInnate immune systemMemory cell potentialEffector CD8T cell fateAcute infectionCell primingInflammatory cytokinesMemory precursorsT-betInterleukin-7IL-7R.Immune systemLow expressionLong-term maintenanceTranscription factorsHomeostatic turnover
2005
Interchromosomal associations between alternatively expressed loci
Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA. Interchromosomal associations between alternatively expressed loci. Nature 2005, 435: 637-645. PMID: 15880101, DOI: 10.1038/nature03574.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsCell NucleusCells, CulturedChromatinChromosome PositioningChromosomes, MammalianCytokinesDeoxyribonuclease IEnhancer Elements, GeneticGene Expression RegulationIn Situ Hybridization, FluorescenceInterferon-gammaInterleukinsLocus Control RegionMiceMice, Inbred C57BLPolymerase Chain ReactionPromoter Regions, GeneticRNA, MessengerTh1 CellsTh2 CellsTranscriptional ActivationConceptsLocus control regionTh2 locus control regionInterchromosomal interactionsDNase I hypersensitive sitesTh2 cytokine locusT cell fateEukaryotic genesIntrachromosomal interactionsChromatin conformationInterchromosomal associationsCytokine genesDifferent chromosomesGene activationSeparate chromosomesControl regionRegulatory regionsHypersensitive sitesCytokine locusTh2 cytokine genesChromosome 10Gene expressionPromoter regionChromosome 11GenesFunctional consequences
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