2019
Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2018
Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Sumida T, Lincoln MR, Ukeje CM, Rodriguez DM, Akazawa H, Noda T, Naito AT, Komuro I, Dominguez-Villar M, Hafler DA. Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity. Nature Immunology 2018, 19: 1391-1402. PMID: 30374130, PMCID: PMC6240373, DOI: 10.1038/s41590-018-0236-6.Peer-Reviewed Original ResearchConceptsProstaglandin E receptor 2Regulatory T cellsTreg cellsT cellsAnti-inflammatory cytokine productionIL-10 productionPeripheral immune toleranceIL-10 expressionΒ-cateninE receptor 2Treg subpopulationsTreg phenotypeIL-10Cytokines IFNImmune toleranceTreg signatureCytokine signatureMultiple sclerosisAutoimmune diseasesCytokine productionInflammatory environmentLethal autoimmunityReceptor 2Activated β-cateninIFN
2014
Decreased 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 HypersensitivityT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTh1-Th2 BalanceConceptsTreg 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 responseSmall-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms
Xiao S, Yosef N, Yang J, Wang Y, Zhou L, Zhu C, Wu C, Baloglu E, Schmidt D, Ramesh R, Lobera M, Sundrud MS, Tsai PY, Xiang Z, Wang J, Xu Y, Lin X, Kretschmer K, Rahl PB, Young RA, Zhong Z, Hafler DA, Regev A, Ghosh S, Marson A, Kuchroo VK. Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms. Immunity 2014, 40: 477-489. PMID: 24745332, PMCID: PMC4066874, DOI: 10.1016/j.immuni.2014.04.004.Peer-Reviewed Original ResearchMeSH KeywordsAndrostenolsAnimalsBenzeneacetamidesBenzhydryl CompoundsCell DifferentiationCell Line, TumorCell LineageCytokinesDigoxinEncephalomyelitis, Autoimmune, ExperimentalGene Regulatory NetworksHeterocyclic Compounds, 4 or More RingsHumansMiceMice, Inbred C57BLMice, KnockoutMultiple SclerosisMyelin-Oligodendrocyte GlycoproteinNuclear Receptor Subfamily 1, Group F, Member 3Peptide FragmentsProtein BindingStructure-Activity RelationshipSystems BiologyTh17 CellsT-Lymphocyte SubsetsTranscription, GeneticTranscriptional ActivationConceptsTranscriptional networksSignature genesCis-regulatory sitesStrong transcriptional effectsInterconnected regulatory networkCell signature genesSystem-scale analysisTranscriptional regulationDirect repressorTarget lociTranscriptome sequencingRegulatory networksDNA bindingTranscriptional effectsCell lineagesCell differentiationT-cell lineageDirect activatorDivergent mechanismsT cell differentiationSpecific inhibitorDistinct mechanismsPotential therapeutic compoundsGenesRetinoid-related orphan receptor gamma t
2013
Microbial Reprogramming Inhibits Western Diet-Associated Obesity
Poutahidis T, Kleinewietfeld M, Smillie C, Levkovich T, Perrotta A, Bhela S, Varian BJ, Ibrahim YM, Lakritz JR, Kearney SM, Chatzigiagkos A, Hafler DA, Alm EJ, Erdman SE. Microbial Reprogramming Inhibits Western Diet-Associated Obesity. PLOS ONE 2013, 8: e68596. PMID: 23874682, PMCID: PMC3707834, DOI: 10.1371/journal.pone.0068596.Peer-Reviewed Original ResearchConceptsAge-associated weight gainWeight gainT cellsFast foodAd libitum caloric intakeActive immune toleranceImmune cell profilesRegulatory T cellsT cell balanceRecent epidemiological studiesLikelihood of obesityNaïve recipient animalsGut microbial ecologyT helperImmune toleranceBaseline dietWeight managementCaloric intakePopulation-based approachMouse modelCell balanceEpidemiological studiesRecipient animalsAnimal modelsAbdominal fatSodium 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
2005
High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model
Ellmerich S, Mycko M, Takacs K, Waldner H, Wahid FN, Boyton RJ, King RH, Smith PA, Amor S, Herlihy AH, Hewitt RE, Jutton M, Price DA, Hafler DA, Kuchroo VK, Altmann DM. High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model. The Journal Of Immunology 2005, 174: 1938-1946. PMID: 15699121, DOI: 10.4049/jimmunol.174.4.1938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationCell MovementCentral Nervous SystemDisease Models, AnimalDisease ProgressionDNA-Binding ProteinsEpitopes, T-LymphocyteHLA-DR AntigensHLA-DR Serological SubtypesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMultiple SclerosisMyelin Basic ProteinParalysisPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell responsesHLA-DR15Multiple sclerosisDeterminant spreadSpontaneous diseaseCell responsesCD4 T cell recognitionCNS tissue damageHuman multiple sclerosisMultiple sclerosis modelT cell reactivityExperimental allergic encephalomyelitisMyelin oligodendrocyte glycoproteinT cell recognitionMyelin basic proteinAllergic encephalomyelitisMyelin epitopesPeptide immunotherapyAxonal degenerationCell reactivityOligodendrocyte glycoproteinPathogenic roleT cellsHigh incidenceTransgenic mice
2000
Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate
Duda P, Krieger J, Schmied M, Balentine C, Hafler D. Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate. The Journal Of Immunology 2000, 165: 7300-7307. PMID: 11120865, DOI: 10.4049/jimmunol.165.12.7300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCD4-Positive T-LymphocytesCell Line, TransformedCell SeparationClone CellsDose-Response Relationship, ImmunologicFemaleGlatiramer AcetateHematopoietic Stem CellsHLA-DR AntigensHumansImmunizationImmunologic MemoryImmunomagnetic SeparationInfant, NewbornLeukocytes, MononuclearLymphocyte ActivationLymphocyte CountMiceMice, Inbred BALB CMice, Inbred C57BLMultiple Sclerosis, Relapsing-RemittingPeptidesSpleenTh1 CellsTh2 CellsConceptsT cell populationsHLA class II DRGlatiramer acetateT cell proliferationClass II DRII DRT cellsCD4 T cell reactivityGA-reactive T cellsHuman T cell proliferative responsesT cell precursor frequencyCell populationsSpecific human T cell clonesT cell proliferative responsesHuman T cell clonesMemory T cellsT cell reactivityMultiple sclerosis patientsRecent clinical findingsCell precursor frequencyCell proliferative responsesCell proliferationT cell clonesDose-dependent proliferationHealthy human adults
1997
B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.
Greenfield EA, Howard E, Paradis T, Nguyen K, Benazzo F, McLean P, Höllsberg P, Davis G, Hafler DA, Sharpe AH, Freeman GJ, Kuchroo VK. B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors. The Journal Of Immunology 1997, 158: 2025-34. PMID: 9036945, DOI: 10.4049/jimmunol.158.5.2025.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAnimalsAntigens, CDAntigens, DifferentiationB7-2 AntigenCD28 AntigensCell DivisionCTLA-4 AntigenFemaleImmunoconjugatesLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLProtein BindingThymomaThymus NeoplasmsT-LymphocytesTransfectionTumor Cells, Cultured
1984
Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes
Tardieu M, Powers M, Hafler D, Hauser S, Weiner H. Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes. European Journal Of Immunology 1984, 14: 561-565. PMID: 6329771, DOI: 10.1002/eji.1830140614.Peer-Reviewed Original ResearchConceptsNormal tissuesMonoclonal antibodiesViral infectionOnly virusInfection of miceUninfected control animalsAdult C57BL/6 miceAutoreactive monoclonal antibodiesNS1 myeloma cellsReovirus type 3Reovirus type 1Autoimmune responseC57BL/6 miceLung tissueT lymphocytesImmune responseSplenic lymphocytesControl animalsEpendymal cellsViral determinantsMyeloma cellsType 1LymphocytesInfectionReovirus type