2024
The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases
Sumida T, Cheru N, Hafler D. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nature Reviews Immunology 2024, 24: 503-517. PMID: 38374298, PMCID: PMC11216899, DOI: 10.1038/s41577-024-00994-x.Peer-Reviewed Original ResearchTreg cell dysfunctionTreg cellsAutoimmune diseasesCell dysfunctionSuppressive function of Treg cellsDifferentiation of regulatory T cellsFunction of Treg cellsDiscovery of Foxp3Foxp3-independent mechanismsTreg cell suppressionRegulatory T cellsTreg cell functionTranscription factor Foxp3Systemic lupus erythematosusRegulate immune responsesInflammatory bowel diseaseFOXP3 mutationsFoxp3-dependentSystemic autoinflammationRegulatory TIPEX syndromeCell lineage determinationT cellsTregsLupus erythematosus
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-cateninIFNRegulatory T cells in autoimmune disease
Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nature Immunology 2018, 19: 665-673. PMID: 29925983, PMCID: PMC7882196, DOI: 10.1038/s41590-018-0120-4.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesTreg cellsRegulatory T cell biologyRegulatory T cellsNon-immune cellsTreg cell plasticityTreg cell biologyNew therapeutic strategiesT cell biologyTreg cell instabilityDisease outcomeT cellsTherapeutic strategiesDiseaseCell plasticityCell biologyCellsAutoimmunityPathogenesisSpecific tissues
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 functionRegulatory T cells in autoimmune neuroinflammation
Kleinewietfeld M, Hafler DA. Regulatory T cells in autoimmune neuroinflammation. Immunological Reviews 2014, 259: 231-244. PMID: 24712469, PMCID: PMC3990868, DOI: 10.1111/imr.12169.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT cellsAutoimmune neuroinflammationMultiple sclerosisRegulatory type 1 (Tr1) cellsForkhead box protein 3Natural Treg cellsBox protein 3Experimental animal modelsT helper cell lineagesType 1 cellsTr1 cellsTreg cellsPeripheral toleranceAnimal modelsSpecific subtypesNeuroinflammationProtein 3SubtypesCell typesCell lineagesCellsTregsSclerosisTreg 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
Regulatory T Cells in MS
Gawlik B, Hafler D. Regulatory T Cells in MS. 2013, 27-47. DOI: 10.1007/978-1-4614-7953-6_2.Peer-Reviewed Original ResearchRegulatory T cellsAutoreactive T cellsT cellsCentral nervous systemMultiple sclerosisTreg cellsHealthy individualsPathogenic autoreactive T cellsMultifocal demyelinating diseaseDemyelinating diseaseCNS lesionsMS patientsAutoimmune responseAutoimmune diseasesPeripheral bloodImmune homeostasisImmune responseNervous systemSusceptible individualsProgressive neurodegenerationDiseaseKey regulatorCellsIndividualsHigher number
2011
Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease
Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nature Medicine 2011, 17: 673-675. PMID: 21540856, PMCID: PMC3675886, DOI: 10.1038/nm.2389.Peer-Reviewed Original ResearchConceptsTreg cellsT helper type 1Regulatory T cellsT regulatory (Treg) cellsHelper type 1T helper typeHuman autoimmune diseasesHuman Treg cellsRegulatory cellsIL-12Multiple sclerosisAutoimmune diseasesPeripheral bloodHelper typeT cellsSuppressive activityType 1Functional plasticityConsiderable phenotypicCellsSclerosisIFNDiseaseMiceBlood
2010
FOXP3+ regulatory T cells in the human immune system
Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nature Reviews Immunology 2010, 10: 490-500. PMID: 20559327, DOI: 10.1038/nri2785.Peer-Reviewed Original ResearchConceptsForkhead box P3Human Treg cellsTreg cellsT cellsKey PointsRegulatory T (TReg) cellsTreg cell-based therapyAntitumour immune responseRegulatory T cellsExpression of CD45RAPromising therapeutic perspectiveHuman immune systemAutoimmune pathogenesisDominant toleranceBox P3HLA-DRCell-based therapiesAutoimmune diseasesImmune homeostasisImmune responseImmune diseasesSuppressive functionPotent mediatorCancer growthImmune systemTherapeutic perspectives
2008
Multiple Sclerosis and Regulatory T Cells
Costantino CM, Baecher-Allan C, Hafler DA. Multiple Sclerosis and Regulatory T Cells. Journal Of Clinical Immunology 2008, 28: 697-706. PMID: 18763026, PMCID: PMC2752287, DOI: 10.1007/s10875-008-9236-x.Peer-Reviewed Original ResearchConceptsRegulatory T cellsCentral nervous systemAutoreactive T cellsT cellsAntigen-specific Treg cellsAutoreactive effector T cellsAutoimmune tissue damageFrequency of TregsOrgan-specific autoimmunityEffector T cellsReactive T cellsBlood-brain barrierPathology of MSIntroductionMultiple sclerosisTreg cellsMS patientsPeripheral toleranceChronic inflammationMultiple sclerosisImmune disordersNew therapiesHealthy individualsNervous systemTissue damageDisease modelsMultiple Sclerosis and Regulatory T Cells
Hutton J, Baecher-Allan C, Hafler D. Multiple Sclerosis and Regulatory T Cells. 2008, 265-277. DOI: 10.1007/978-0-387-77909-6_13.Peer-Reviewed Original ResearchRegulatory T cellsAutoreactive T cellsMultiple sclerosisT cellsAntigen-specific Treg cellsImmunopathology of MSCentral nervous system white matterAutoimmune tissue damageFrequency of TregsNervous system white matterOrgan-specific autoimmunityEffector T cellsReactive T cellsImmunosuppressive therapyTreg cellsAutoimmune processMS patientsPeripheral toleranceSpecific autoimmunityImmune disordersNew therapiesHealthy individualsB cellsWhite matterTissue damage
2007
Abnormal Tr1 differentiation in multiple sclerosis
Astier AL, Hafler DA. Abnormal Tr1 differentiation in multiple sclerosis. Journal Of Neuroimmunology 2007, 191: 70-78. PMID: 17936368, PMCID: PMC2200628, DOI: 10.1016/j.jneuroim.2007.09.018.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCentral nervous systemRegulatory T cell defectsInduction of TregsInflammatory demyelinating diseaseIL-10 secretionRegulatory T cellsHuman autoimmune diseasesT cell defectsContext of autoimmunityHigh TregTr1 differentiationTreg activityDemyelinating diseaseTreg cellsImmunosuppressive roleAutoimmune diseasesT cellsNervous systemAltered functionCell defectsSuch diseasesDiseaseTregsSclerosis
2005
Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells
Baecher-Allan C, Wolf E, Hafler DA. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells. Clinical Immunology 2005, 115: 10-18. PMID: 15870015, DOI: 10.1016/j.clim.2005.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, B-LymphocyteCD4-Positive T-LymphocytesCD58 AntigensCoculture TechniquesEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingLeukocyte Common AntigensL-SelectinReceptors, Interleukin-2Receptors, TransferrinT-Lymphocyte SubsetsConceptsCD4 T cellsT cellsTreg cellsRegulatory cellsTotal CD4 T cellsHuman regulatory cellsRegulatory T cellsAutoimmune disease modelsImportance of CD4Regulatory populationImmune homeostasisCD25Suppressive activityCD4Human regulatorySpecific subpopulationsDisease modelsSignificant proportionMiceVivoMurine cellsPotential heterogeneityFuture studiesCellsHuman diseases