2017
Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+ T Cell Terminal Differentiation and Loss of Multipotency
Gray SM, Amezquita RA, Guan T, Kleinstein SH, Kaech SM. Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+ T Cell Terminal Differentiation and Loss of Multipotency. Immunity 2017, 46: 596-608. PMID: 28410989, PMCID: PMC5457165, DOI: 10.1016/j.immuni.2017.03.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationChromatinEnhancer of Zeste Homolog 2 ProteinFlow CytometryForkhead Box Protein O1Gene ExpressionHistonesImmunoblottingImmunologic MemoryLysineMethylationMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalMultipotent Stem CellsPolycomb Repressive Complex 2Reverse Transcriptase Polymerase Chain ReactionConceptsH3K27me3 depositionPolycomb repressive complex 2T cell terminal differentiationRepressive complex 2MP cellsLoss of multipotencyPro-survival genesCell terminal differentiationFate restrictionPermissive chromatinEpigenetic silencingMemory cell potentialDevelopmental plasticityCell developmentTerminal differentiationCell differentiationGenesPrecursor cellsFOXO1 expressionChromatinMemory precursor cellsMultipotencyCell maturationClonal expansionCells
2016
Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells
Rubelt F, Bolen CR, McGuire HM, Heiden J, Gadala-Maria D, Levin M, M. Euskirchen G, Mamedov MR, Swan GE, Dekker CL, Cowell LG, Kleinstein SH, Davis MM. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells. Nature Communications 2016, 7: 11112. PMID: 27005435, PMCID: PMC5191574, DOI: 10.1038/ncomms11112.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesGenes, ImmunoglobulinGenes, T-Cell ReceptorHumansReverse Transcriptase Polymerase Chain ReactionTwins, MonozygoticV(D)J RecombinationConceptsChromosome-wide levelJ gene segmentsAntigen receptor repertoireHeritable mechanismsSingle chromosomeEpigenetic differencesHeritable differencesReceptor repertoireLymphocyte receptor repertoireGene segmentsAdaptive immune systemHeritable factorsRepertoireRelative usageAntigen-experienced cellsThymic selectionCellsImmune systemChromosomesSignificant variationCDR3 regionMonozygotic twinsRearrangementT lymphocyte subsets
2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, Kleinstein SH, Kaech SM. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. Journal Of Experimental Medicine 2015, 212: 2041-2056. PMID: 26503446, PMCID: PMC4647261, DOI: 10.1084/jem.20150186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCluster AnalysisFlow CytometryHomeodomain ProteinsHost-Pathogen InteractionsLectins, C-TypeLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutMice, TransgenicOligonucleotide Array Sequence AnalysisProtein BindingReceptors, ImmunologicRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionT-Box Domain ProteinsT-Lymphocytes, CytotoxicTranscriptomeZinc Finger E-box Binding Homeobox 2ConceptsTerminal differentiationT cell terminal differentiationChromatin immunoprecipitation sequencingNovel genetic pathwaysTranscription factor ZEB2Cell terminal differentiationZeb2 functionImmunoprecipitation sequencingMemory cell potentialDifferentiation programGenetic pathwaysCytotoxic T lymphocyte differentiationTerminal effectorZEB2 mRNAPrecursor cellsCoordinated actionLymphocyte differentiationT lymphocyte differentiationMemory precursor cellsGenesT-betDifferentiationViral infectionZEB2CooperateProduction of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells
Laidlaw BJ, Cui W, Amezquita RA, Gray SM, Guan T, Lu Y, Kobayashi Y, Flavell RA, Kleinstein SH, Craft J, Kaech SM. Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells. Nature Immunology 2015, 16: 871-879. PMID: 26147684, PMCID: PMC4713030, DOI: 10.1038/ni.3224.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesDendritic CellsFlow CytometryGene Expression ProfilingHost-Pathogen InteractionsImmunologic MemoryInflammationInterleukin-10Lymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutReverse Transcriptase Polymerase Chain ReactionT-Lymphocytes, Regulatory
2011
Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis
Protiva P, Mason JB, Liu Z, Hopkins ME, Nelson C, Marshall JR, Lambrecht RW, Pendyala S, Kopelovich L, Kim M, Kleinstein SH, Laird PW, Lipkin M, Holt PR. Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis. Cancer Prevention Research 2011, 4: 530-543. PMID: 21321062, PMCID: PMC3742550, DOI: 10.1158/1940-6207.capr-10-0143.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiological AvailabilityCell Transformation, NeoplasticColonColorectal NeoplasmsDietary SupplementsDNA BreaksDNA MethylationFemaleFolic AcidFolic Acid DeficiencyGene ExpressionGene Expression ProfilingHumansMaleMiddle AgedOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticRectumReverse Transcriptase Polymerase Chain ReactionTumor Suppressor Protein p53ConceptsFolate supplementationFolate deliveryFolate depletionImmune responseColorectal carcinogenesisDNA strand breaksHuman colonColorectal cancer riskFolic acidSupplemental folic acidLow-folate dietLow folate statusImmune response pathwaysImmune-related pathwaysFirst studyRectosigmoid biopsiesRisk volunteersPrimary endpointGene array analysisPromoter-specific DNA methylationRepletion protocolFolate dietFolate levelsSecond studyFolate status
2009
Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells
Bruno VM, Hannemann S, Lara-Tejero M, Flavell RA, Kleinstein SH, Galán JE. Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells. PLOS Pathogens 2009, 5: e1000538. PMID: 19662166, PMCID: PMC2714975, DOI: 10.1371/journal.ppat.1000538.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBlotting, WesternCell LineColitisEpithelial CellsGene ExpressionGene Expression ProfilingGuanine Nucleotide Exchange FactorsHumansImmunity, InnateMiceMitogen-Activated Protein Kinase KinasesMyotonin-Protein KinaseNF-kappa BOligonucleotide Array Sequence AnalysisProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionSalmonella InfectionsSalmonella typhimuriumSignal TransductionTranscription, GeneticConceptsInnate immune receptorsInnate immune responseIntestinal inflammationImmune responseEpithelial cellsBacterial productsIntestinal inflammatory pathologyImmune receptorsCultured epithelial cellsEnteric pathogen Salmonella typhimuriumInnate immune systemIntestinal epithelial cellsInflammatory pathologyInflammatory responseType III secretion effectorsImmune systemSalmonella typhimuriumNF-kappaBMitogen-activated protein kinaseEnteric pathogensPathogen Salmonella typhimuriumPathologyReceptorsInflammationType III secretion system