2015
Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli
Housley WJ, Fernandez SD, Vera K, Murikinati SR, Grutzendler J, Cuerdon N, Glick L, De Jager PL, Mitrovic M, Cotsapas C, Hafler DA. Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli. Science Translational Medicine 2015, 7: 291ra93. PMID: 26062845, PMCID: PMC4574294, DOI: 10.1126/scitranslmed.aaa9223.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAllelesAutoimmunityCase-Control StudiesCD4-Positive T-LymphocytesCell NucleusCytokinesFemaleGenetic Predisposition to DiseaseHumansInflammationMaleMiddle AgedMultiple SclerosisNF-kappa BPolymorphism, Single NucleotideProtein TransportReceptors, Tumor Necrosis Factor, Type IRisk FactorsSex CharacteristicsSignal TransductionTime FactorsTumor Necrosis Factor-alphaConceptsB-cell leukemia 3Multiple sclerosisNegative regulatorInflammatory stimuliGenetic variantsWide association studyDisease susceptibility variantsNaïve CD4 T cellsRapid genetic screeningCD4 T cellsActivation of p65Transcription factor nuclear factor κBExpression of NFκBNuclear factor κBApoptosis 1Cellular inhibitorGG risk genotypeDegradation of inhibitorCentral regulatorAssociation studiesCytokine blockadeUlcerative colitisAutoimmune diseasesTumor necrosisSusceptibility variants
2014
Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults
Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, Belshe RB, Hafler DA, Kaech SM, Kleinstein SH, Trentalange M, Allore HG, Shaw AC. Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults. The Journal Of Infectious Diseases 2014, 211: 1174-1184. PMID: 25367297, PMCID: PMC4366602, DOI: 10.1093/infdis/jiu573.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedCytokinesDual Specificity Phosphatase 1FemaleGene Expression RegulationGPI-Linked ProteinsHumansImmunity, InnateInfluenza VaccinesInfluenza, HumanInterleukin-10Interleukin-6Lipopolysaccharide ReceptorsMaleMonocytesPhosphorylationReceptors, IgGSignal TransductionSTAT3 Transcription FactorTumor Necrosis Factor-alphaVaccinationYoung AdultConceptsOlder adultsInfluenza vaccinationInflammatory monocytesInterleukin-10Cytokine productionOlder subjectsAnti-inflammatory cytokine interleukin-10Influenza vaccine antibody responseTumor necrosis factor αImpaired vaccine responsesVaccine antibody responseIL-10 productionCytokine interleukin-10Proinflammatory cytokine productionNecrosis factor αAge-associated elevationPhosphorylated signal transducerVaccine responsesAntibody responseInterleukin-6Immune responseMonocyte populationsDay 28Intracellular stainingVaccination
2013
Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus
Ottoboni L, Frohlich IY, Lee M, Healy BC, Keenan BT, Xia Z, Chitnis T, Guttmann CR, Khoury SJ, Weiner HL, Hafler DA, De Jager PL. Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus. Neurology 2013, 81: 1891-1899. PMID: 24174586, PMCID: PMC3843384, DOI: 10.1212/01.wnl.0000436612.66328.8a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginineChemokine CXCL10FemaleGene Expression RegulationGenetic Predisposition to DiseaseGenotypeGlutamineHEK293 CellsHumansImmunologic FactorsLongitudinal StudiesMaleMonocytesMultiple SclerosisMutationPhorbol EstersReceptors, Tumor Necrosis Factor, Type IRNA IsoformsSignal TransductionTumor Necrosis Factor-alphaConceptsTNFRSF1A locusSusceptibility allelesFunctional consequencesRobust transcriptional responseTranscriptional responseCytoplasmic domainRNA isoformsTNF-α stimulationRho GTPaseMS susceptibility genesMS geneG proteinsSusceptibility genesMolecular levelTNF pathwayGenesAltered expressionLociTNF-α pathwayAllelesRisk allelesPathwayGTPaseImmune functionTransmembraneSodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells
Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 2013, 496: 518-522. PMID: 23467095, PMCID: PMC3746493, DOI: 10.1038/nature11868.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalGene SilencingGranulocyte-Macrophage Colony-Stimulating FactorHumansImmediate-Early ProteinsInterleukin-2MAP Kinase Signaling SystemMiceMice, Inbred C57BLP38 Mitogen-Activated Protein KinasesPhenotypeProtein Serine-Threonine KinasesSodium Chloride, DietaryTh17 CellsTranscription FactorsTumor Necrosis Factor-alpha
2006
Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response
Karni A, Abraham M, Monsonego A, Cai G, Freeman GJ, Hafler D, Khoury SJ, Weiner HL. Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response. The Journal Of Immunology 2006, 177: 4196-4202. PMID: 16951385, DOI: 10.4049/jimmunol.177.6.4196.Peer-Reviewed Original ResearchConceptsMyeloid dendritic cellsDendritic cellsMultiple sclerosisInnate immune systemRR-MSImmune responseImmune systemT cell-mediated autoimmune diseaseSecondary progressive multiple sclerosisCell-mediated autoimmune diseaseStages of MSIncreased percentageProgressive phaseNeuronal degenerative changesSecondary progressive phaseSP-MS patientsProgressive multiple sclerosisProinflammatory immune responsePrimary immune responseNaive T cellsImmunologic basisTh1 responseClinical patternMS patientsPD-L1
2000
A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatients
1992
CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production.
Freeman GJ, Lombard DB, Gimmi CD, Brod SA, Lee K, Laning JC, Hafler DA, Dorf ME, Gray GS, Reiser H. CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. The Journal Of Immunology 1992, 149: 3795-801. PMID: 1281186, DOI: 10.4049/jimmunol.149.12.3795.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationAntigens, Differentiation, T-LymphocyteAntigens, SurfaceB7-1 AntigenBase SequenceBlotting, NorthernCD28 AntigensCell Adhesion MoleculesCell LineCTLA-4 AntigenHumansImmunoconjugatesInterferon-gammaInterleukinsLeukemia, T-CellLymphocyte ActivationLymphokinesMiceMolecular Sequence DataOligonucleotide ProbesPolymerase Chain ReactionRNA, MessengerT-LymphocytesTumor Necrosis Factor-alphaConceptsT cell clonesCTLA-4 mRNACTLA-4T cellsActivated T cellsT cell activationT cell linesMurine T cell clonesCell clonesCD28 mRNACostimulatory signalsT cell receptor-dependent stimulationCell activationNormal T cell subsetsAg-presenting cellsHuman T cell clonesT cell subsetsExpression of CD28Th2 cytokine profileMost T cellsLeukemic T cell lineCell linesReceptor-dependent stimulationSuch costimulatory signalsInteraction of B7
1991
Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease.
Brod SA, Benjamin D, Hafler DA. Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease. The Journal Of Immunology 1991, 147: 810-5. PMID: 1907306, DOI: 10.4049/jimmunol.147.3.810.Peer-Reviewed Original ResearchConceptsPeripheral bloodCSF of subjectsIL-5 mRNAT cell clonesIFN-gamma mRNAIL-4Inflammatory diseasesIFN-gammaIL-2Systemic inflammationT cellsTh1 T cell clonesTh2-type T cellsT cell cytokine profilesIL-2/ILDistinct T cell populationsCell clonesT cell populationsT cell expressionType T cellsTNF-alpha mRNAHuman inflammatory diseasesIL-2 mRNACytokine profileImmune compartmentInterleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis
Hafler D, Chofflon M, Kurt-Jones E, Weiner H. Interleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis. Clinical Immunology 1991, 58: 115-125. PMID: 1670583, DOI: 10.1016/0090-1229(91)90153-2.Peer-Reviewed Original ResearchConceptsAutologous mixed lymphocyte reactionMultiple sclerosisWhole T cellsMS patientsT cellsImmune defectsChronic progressive multiple sclerosisNon-T cell populationsAutologous mixed lymphocyte responseProgressive multiple sclerosisMixed lymphocyte responseMixed lymphocyte reactionResponse of CD4T cell populationsSex-matched controlsT cell regulationIL-1 secretionCell populationsLymphokine IFN-gammaImmunoregulatory defectsLymphocyte responsesRIL-2Lymphocyte reactionMS subjectsAutoimmune diseases