2017
Podoplanin is a negative regulator of Th17 inflammation
Nylander AN, Ponath GD, Axisa PP, Mubarak M, Tomayko M, Kuchroo VK, Pitt D, Hafler DA. Podoplanin is a negative regulator of Th17 inflammation. JCI Insight 2017, 2: e92321. PMID: 28878118, PMCID: PMC5621890, DOI: 10.1172/jci.insight.92321.Peer-Reviewed Original ResearchConceptsT cellsIL-17IL-17 secretionDistinct cytokine profilesInflammatory gene signatureTh17-polarizing conditionsTh17 cellsCytokine profileCell subsetsInflammatory responseSkin biopsiesMouse modelPDPN expressionMultiple organsSkin diseasesGene signatureInflammationLymphatic systemCLEC-2PDPNRecent dataDifferent subpopulationsCellsTranscriptional profilesShRNA gene
2015
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjects
2014
Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells
Gautron A, Dominguez-Villar M, de Marcken M, Hafler DA. Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells. European Journal Of Immunology 2014, 44: 2703-2711. PMID: 24838857, PMCID: PMC4165702, DOI: 10.1002/eji.201344392.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCell DifferentiationCTLA-4 AntigenFemaleForkhead Transcription FactorsGene Expression RegulationGranzymesHepatitis A Virus Cellular Receptor 2HumansInterleukin 1 Receptor Antagonist ProteinInterleukin-10InterleukinsLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceMinor Histocompatibility AntigensReceptors, CCR6STAT3 Transcription FactorTh17 CellsT-Lymphocytes, RegulatoryConceptsTim-3 expressionRegulatory T cellsTreg cellsTim-3T cellsNatural regulatory T cellsMucin domain 3Number of TIMTh17 cell responseEffector T cellsT cell suppressionHuman Treg cellsT-cell immunoglobulinAnti-CD28 stimulationT cell differentiationSTAT-3 expressionPathogenic Th1Th17 cellsTc1 cellsImmune toleranceTh1 cellsLevel of expressionReduced gene expressionGene expressionSuppressor functionSP0104 The Molecular Basis of Autoimmune Disease
Hafler D. SP0104 The Molecular Basis of Autoimmune Disease. Annals Of The Rheumatic Diseases 2014, 73: 27. DOI: 10.1136/annrheumdis-2014-eular.6254.Peer-Reviewed Original ResearchGenome-wide association studiesNon-coding regionsConsensus transcription factorNumerous genetic associationsDistinct cell typesDifferent autoimmune diseasesAutoimmune diseasesChromatin mapsTh17 cellsGWAS hitsHigh NaCl levelsTranscription factorsDNA sequencesMolecular basisGenetic dataCausal mutationsDisease riskAssociation studiesMechanistic basisCommon SNPsNucleotide variantsAP-1Risk SNPsCell typesSpecific disruptionDecreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells
Kofler DM, Marson A, Dominguez-Villar M, Xiao S, Kuchroo VK, Hafler DA. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. Journal Of Clinical Investigation 2014, 124: 2513-2522. PMID: 24812667, PMCID: PMC4089462, DOI: 10.1172/jci72973.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAutoimmunityCase-Control StudiesDinoprostoneDown-RegulationFemaleGene Knockdown TechniquesGene SilencingHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedModels, ImmunologicalMultiple SclerosisNuclear Receptor Subfamily 1, Group F, Member 3PhenotypePromoter Regions, GeneticReceptors, Prostaglandin E, EP2 SubtypeSignal TransductionTh17 CellsConceptsTh17 cell phenotypeProstaglandin receptor EP2Receptor EP2Healthy individualsOverexpression of EP2Transcription factor RORCT cell subsetsEffects of PGE2Cell phenotypeExpression of IFNInflammatory gene transcriptionPGE2-dependent pathwayTh17 cellsWT miceAutoimmune diseasesCell subsetsHealthy subjectsEP2 expressionGM-CSFEP2RORCCD4Cell typesCellsGene transcriptionTreg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40: 569-581. PMID: 24745333, PMCID: PMC4070748, DOI: 10.1016/j.immuni.2014.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedCytokinesEosinophilsFibrinogenForkhead Transcription FactorsGene Expression ProfilingGene Expression RegulationImmunosuppression TherapyLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, ImmunologicRespiratory HypersensitivityTh1-Th2 BalanceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsTreg cell subsetsTh2 cell responsesTreg cellsCell subsetsCell responsesProinflammatory T helper 1T effector cell proliferationTreg cell-mediated suppressionFibrinogen-like protein 2Allergic airway inflammationT regulatory (Treg) cellsTh2 cytokine productionSuppression of Th1T helper 1Effector cell proliferationTreg signature genesProinflammatory Th1TIGIT expressionAirway inflammationTh17 cellsRegulatory cellsHelper 1Cytokine productionT cellsImmune response
2013
The plasticity of human Treg and Th17 cells and its role in autoimmunity
Kleinewietfeld M, Hafler DA. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Seminars In Immunology 2013, 25: 305-312. PMID: 24211039, PMCID: PMC3905679, DOI: 10.1016/j.smim.2013.10.009.Peer-Reviewed Original ResearchConceptsTh17 cellsT cellsMultiple sclerosisAutoimmune diseasesImmune systemPlasticity of TregsEffector T cellsRegulatory T cellsEffector cell populationsHuman autoimmune diseasesT cell subpopulationsT helper cellsParticular multiple sclerosisT cell plasticityHigh gradeInnate immune systemAdaptive immune systemStrength of stimulationT cell developmentHuman TregsHelper cellsImmune responseImmune reactionsNaive cellsTregsThe CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans
Lozano E, Joller N, Cao Y, Kuchroo VK, Hafler DA. The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans. The Journal Of Immunology 2013, 191: 3673-3680. PMID: 23980210, PMCID: PMC3819731, DOI: 10.4049/jimmunol.1300945.Peer-Reviewed Original ResearchConceptsNaive T cellsT cellsInflammatory balanceIL-13IL-17-producing cellsRole of CD226IL-17 productionIL-17 secretionHuman autoimmune diseasesIFN-γ productionIL-13 secretionIFN-γ expressionProduction of IFNSTAT-6 phosphorylationT cell activationHuman T cellsLigand CD155Th17 cellsIL-17Autoimmune diseasesIL-4T-betTh1 differentiationTh17 conditionsTherapeutic approachesSodium 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-alphaHigh Dietary Salt Aggravates Experimental Neuroinflammation in Mice Via Induction of Th17 Cells (IN9-2.005)
Linker R, Manzel A, Kleinewietfeld M, Hafler D, Muller D. High Dietary Salt Aggravates Experimental Neuroinflammation in Mice Via Induction of Th17 Cells (IN9-2.005). Neurology 2013, 80 DOI: 10.1212/wnl.80.7_supplement.in9-2.005.Peer-Reviewed Original ResearchHigh Dietary Salt Aggravates Experimental Neuroinflammation in Mice Via Induction of Th17 Cells (S50.003)
Linker R, Manzel A, Kleinewietfeld M, Hafler D, Muller D. High Dietary Salt Aggravates Experimental Neuroinflammation in Mice Via Induction of Th17 Cells (S50.003). Neurology 2013, 80 DOI: 10.1212/wnl.80.7_supplement.s50.003.Peer-Reviewed Original Research
2012
Induction and molecular signature of pathogenic TH17 cells
Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, Wu C, Kleinewietfeld M, Kunder S, Hafler DA, Sobel RA, Regev A, Kuchroo VK. Induction and molecular signature of pathogenic TH17 cells. Nature Immunology 2012, 13: 991-999. PMID: 22961052, PMCID: PMC3459594, DOI: 10.1038/ni.2416.Peer-Reviewed Original ResearchHigh salt induces pathogenic Th17 cells and exacerbates autoimmune diseases (60.13)
Kleinewietfeld M, Manzel A, Wu C, Titze J, Kuchroo V, Linker R, Muller D, Hafler D. High salt induces pathogenic Th17 cells and exacerbates autoimmune diseases (60.13). The Journal Of Immunology 2012, 188: 60.13-60.13. DOI: 10.4049/jimmunol.188.supp.60.13.Peer-Reviewed Original ResearchPathogenic Th17 cellsExperimental autoimmune encephalomyelitisEnvironmental risk factorsTh17 cellsAutoimmune diseasesRisk factorsMultiple sclerosisHigh-salt dietHelper T cellsGenetic risk factorsExacerbated inductionAutoimmune encephalomyelitisSalt dietSalt intakeCardiovascular diseaseT cellsSun exposureSevere formDiseaseGenetic factorsDietCertain pathogensInduction of murineInductionPivotal role
2010
TGF-β Induces IL-9 Production from Human Th17 Cells
Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA. TGF-β Induces IL-9 Production from Human Th17 Cells. The Journal Of Immunology 2010, 185: 46-54. PMID: 20498357, PMCID: PMC2936106, DOI: 10.4049/jimmunol.1000356.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell PolarityCells, CulturedCoculture TechniquesDiabetes Mellitus, Type 1Gene Expression RegulationHumansImmunohistochemistryInflammation MediatorsInterleukin-17Interleukin-9Middle AgedResting Phase, Cell CycleT-Lymphocytes, Helper-InducerTransforming Growth Factor beta1Young AdultConceptsCD4 T cellsIL-9 productionIL-17IL-9IL-1betaCD4 cellsProinflammatory cytokinesT cellsNaive cellsIL-9/ILCD4 T cell subsetsMemory CD4 T cellsNaive CD4 T cellsHuman naive CD4 T cellsTh17-inducing cytokinesT cell subsetsHuman autoimmune diseasesAutoimmune diabetesMemory CD4Th17 cellsTh2 cytokinesAutoimmune diseasesCell subsetsIL-4Inflammatory conditions
2009
TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. European Journal Of Immunology 2009, 39: 2492-2501. PMID: 19676072, PMCID: PMC2759376, DOI: 10.1002/eji.200939274.Peer-Reviewed Original Research
2008
IL-21 and TGF-β are required for differentiation of human TH17 cells
Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature 2008, 454: 350-352. PMID: 18469800, PMCID: PMC2760130, DOI: 10.1038/nature07021.Peer-Reviewed Original Research