2023
Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs
Côrte-Real B, Hamad I, Arroyo Hornero R, Geisberger S, Roels J, Van Zeebroeck L, Dyczko A, van Gisbergen M, Kurniawan H, Wagner A, Yosef N, Weiss S, Schmetterer K, Schröder A, Krampert L, Haase S, Bartolomaeus H, Hellings N, Saeys Y, Dubois L, Brenner D, Kempa S, Hafler D, Stegbauer J, Linker R, Jantsch J, Müller D, Kleinewietfeld M. Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. Cell Metabolism 2023, 35: 299-315.e8. PMID: 36754020, DOI: 10.1016/j.cmet.2023.01.009.Peer-Reviewed Original ResearchConceptsHuman TregsPro-inflammatory featuresLong-term dysfunctionPro-inflammatory signatureMetabolic reprogrammingLong-term functionDysfunctional TregsFoxp3 downregulationPeripheral toleranceMitochondrial respirationMetabolic disturbancesTregsImmune functionAutoimmunityMetabolic fitnessIntracellular NaMitochondrial NaHigh saltMitochondrial metabolismElectron transport chainTranscriptional changesFoxp3DysfunctionBlockade
2014
Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes. Science 2014, 344: 519-523. PMID: 24786080, PMCID: PMC4910825, DOI: 10.1126/science.1249547.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAllelesAlzheimer DiseaseAutoimmune DiseasesAutoimmunityCD4-Positive T-LymphocytesEthnicityGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunity, InnateMonocytesMultiple SclerosisNeurodegenerative DiseasesParkinson DiseasePolymorphism, Single NucleotideQuantitative Trait LociRheumatic FeverTranscriptomeConceptsSpecific immune cell typesHuman immune functionImmune cell typesMulti-ethnic cohortCell-autonomous effectsAutoimmune diseasesT cellsImmune functionParkinson's diseaseHealthy individualsInnate immunityRisk allelesDiseaseExpression quantitative trait loci (eQTL) studiesQuantitative trait loci studiesSusceptibility allelesPutative functional assignmentsCausal regulatory variantsDisease-associated lociDisease susceptibility variantsCell typesSusceptibility variantsTrans-eQTLsFunctional assignmentRegulatory variants
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 functionTransmembrane
2009
IL-17–producing human peripheral regulatory T cells retain suppressive function
Beriou G, Costantino CM, Ashley CW, Yang L, Kuchroo VK, Baecher-Allan C, Hafler DA. IL-17–producing human peripheral regulatory T cells retain suppressive function. Blood 2009, 113: 4240-4249. PMID: 19171879, PMCID: PMC2676084, DOI: 10.1182/blood-2008-10-183251.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDEnzyme-Linked Immunosorbent AssayFlow CytometryForkhead Transcription FactorsHLA-DR AntigensHumansImmune ToleranceInterleukin-17Interleukin-1betaInterleukin-6Lymphocyte ActivationReverse Transcriptase Polymerase Chain ReactionT-LymphocytesT-Lymphocytes, RegulatoryTransforming Growth Factor betaConceptsRegulatory T cellsIL-17Suppressive functionTreg clonesT cellsPeripheral regulatory T cellsProinflammatory cytokines IL-1betaSustained Foxp3 expressionIL-17 productionIL-17 secretionCytokines IL-1betaAutoimmune pathogenesisEffector cellsInterleukin-17Foxp3 expressionHuman TregsInflammatory milieuIL-6IL-1betaInflammatory conditionsImmune functionSuppressive activityTregsCellsRecent studies
1991
Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases
Miller A, Hafler D, Weiner H. Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. The FASEB Journal 1991, 5: 2560-2566. PMID: 1868980, DOI: 10.1096/fasebj.5.11.1868980.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisAutoimmune diseasesAnimal model experimental autoimmune encephalomyelitisModel experimental autoimmune encephalomyelitisHuman disease multiple sclerosisSpecific immune interventionAutoimmune T cellsHuman autoimmune diseasesNormal immune systemDisease multiple sclerosisMajor histocompatibility complexImmunospecific therapyTrimolecular complexImmune interventionSelective immunotherapyMultiple sclerosisT cellsImmune functionNonspecific modulationImmune systemAntigen recognitionHistocompatibility complexSuppressor mechanismDiseaseImmunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis
Hafler D, Orav J, Gertz R, Stazzone L, Weiner H. Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis. Journal Of Neuroimmunology 1991, 32: 149-158. PMID: 1672870, DOI: 10.1016/0165-5728(91)90007-t.Peer-Reviewed Original ResearchConceptsT cell populationsDisability Status ScaleMixed lymphocyte reactionSpontaneous proliferationT cellsImmune measuresACTH infusionImmune functionChronic progressive multiple sclerosisProgressive multiple sclerosis patientsCD4/CD8 ratioCell populationsAllogeneic mixed lymphocyte reactionFunctional immune measuresPeripheral blood CD4Progressive multiple sclerosisPositive clinical responsePositive T cellsMultiple sclerosis patientsFunctional immune assaysLevels of proliferationBlood CD4CD8 ratioClinical improvementClinical response
1990
T‐T cell interactions are mediated by adhesion molecules
Brod S, Purvee M, Benjamin D, Hafler D. T‐T cell interactions are mediated by adhesion molecules. European Journal Of Immunology 1990, 20: 2259-2268. PMID: 1700751, DOI: 10.1002/eji.1830201015.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCD3 ComplexCD58 AntigensCell Adhesion MoleculesCell CommunicationClone CellsHumansImmunophenotypingInterleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMitogensReceptors, Antigen, T-CellT-LymphocytesConceptsT cell clonesAutologous T cell clonesPeripheral blood T cellsAdhesion molecules LFA-1Blood T cellsT cellsLFA-3Major histocompatibility complexInflammatory responseCell clonesICAM-1LFA-1T cell immune functionCD3/T cell receptor complexSpecific T cellsCell adhesion molecules LFA-1Cell immune functionT cell interactionsT cell activationT cell receptor complexMHC determinantsCell receptor complexImmune functionCell activationCD2 pathway
1988
Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody.
Borst J, van Dongen JJ, Bolhuis RL, Peters PJ, Hafler DA, de Vries E, van de Griend RJ. Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody. Journal Of Experimental Medicine 1988, 167: 1625-1644. PMID: 2966845, PMCID: PMC2188932, DOI: 10.1084/jem.167.5.1625.Peer-Reviewed Original ResearchConceptsTCR gamma/deltaT lymphocytesPeripheral bloodHuman TCR-gamma/deltaT cell receptor gamma/deltaGrowth factorGamma/deltaViable T cellsT cell clonesDistinct immune functionsTarget cell recognitionDifferent receptor typesHuman T lymphocytesCD8 antigenDelta antibodyIL-2Murine T lymphocytesT cellsCell surface iodinationCytolytic activityImmune functionReceptor typesLymphocytesTCR moleculesNormal individuals
1984
Altered blood T-cell subsets in patients with multiple sclerosis
Weiner H, Hafler D, Fallis R, Johnson D, Ault K, Hauser S. Altered blood T-cell subsets in patients with multiple sclerosis. Journal Of Neuroimmunology 1984, 6: 115-121. PMID: 6373819, DOI: 10.1016/0165-5728(84)90032-8.Peer-Reviewed Original ResearchConceptsT cell subsetsMultiple sclerosisBlood T cell subsetsChronic progressive patientsActive multiple sclerosisStage of illnessSpontaneous immunoglobulin productionCentral nervous systemImmunoregulatory abnormalitiesT8 ratioActive diseaseDisease activityProgressive patientsAcute patientsPeripheral bloodImmunoglobulin productionImmune functionPatientsNervous systemSclerosisSpinal fluidDiagnostic testsAbnormalitiesVariety of protocolsPleocytosis