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
2016
AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease
Kitz A, de Marcken M, Gautron AS, Mitrovic M, Hafler DA, Dominguez-Villar M. AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease. EMBO Reports 2016, 17: 1169-1183. PMID: 27312110, PMCID: PMC4967959, DOI: 10.15252/embr.201541905.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune DiseasesBiomarkersCell DifferentiationCytokinesForkhead Transcription FactorsGene Expression ProfilingGene SilencingHumansImmunomodulationInterferon-gammaPhenotypePhosphatidylinositol 3-KinasesProtein IsoformsProto-Oncogene Proteins c-aktSignal TransductionT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscriptomeConceptsAutoimmune diseasesIFNγ secretionHuman TregsGenome-wide gene expression approachUntreated relapsing-remitting MS patientsRelapsing-remitting MS patientsImmune suppressive functionHuman autoimmune diseasesT helper 1Inflammatory cytokines IFNγTreg suppressor functionNovel treatment paradigmEffector phenotypeMS patientsTreg generationCytokines IFNγHelper 1Multiple sclerosisTreatment paradigmSuppressive functionTregsVivo modelDiseaseSecretionSuppressor functionPD-1 marks dysfunctional regulatory T cells in malignant gliomas
Lowther DE, Goods BA, Lucca LE, Lerner BA, Raddassi K, van Dijk D, Hernandez AL, Duan X, Gunel M, Coric V, Krishnaswamy S, Love JC, Hafler DA. PD-1 marks dysfunctional regulatory T cells in malignant gliomas. JCI Insight 2016, 1: e85935. PMID: 27182555, PMCID: PMC4864991, DOI: 10.1172/jci.insight.85935.Peer-Reviewed Original ResearchTumor-infiltrating TregsPD-1IFN-γ productionGlioblastoma multiformeT cellsImmune responseHealthy subjectsDysfunctional regulatory T cellsHigh PD-1 expressionCell death protein 1PD-1-blocking antibodiesPD-1 expressionEffector T cellsRegulatory T cellsDeath protein 1Antitumoral immune responseImmune checkpoint receptorsProduction of IFNExhausted phenotypeExhaustion signaturesCheckpoint receptorsHuman TregsTumor infiltratesFunctional statusMalignant gliomas
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 cellsTregs
2011
CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis
Baecher-Allan CM, Costantino CM, Cvetanovich GL, Ashley CW, Beriou G, Dominguez-Villar M, Hafler DA. CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 186: 3317-3326. PMID: 21300823, PMCID: PMC4467560, DOI: 10.4049/jimmunol.1002502.Peer-Reviewed Original ResearchMeSH KeywordsAdultCD2 AntigensCD4 AntigensCell DifferentiationCells, CulturedCoculture TechniquesFetal BloodForkhead Transcription FactorsHumansInfant, NewbornInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLymphocyte ActivationMiddle AgedMultiple SclerosisSignal TransductionT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryYoung AdultConceptsMultiple sclerosisIL-17Suppressive capacityDR cellsRegulatory T cell populationEffector T cellsExpression of CD127T cell populationsMechanism of actionTreg populationRegulatory cellsIL-10Effector cellsHLA-DREffector subsetsHuman TregsCD2 costimulationMemory TregsT cellsTregsAdult bloodLow expressionSclerosisPatientsCD127
2010
Human regulatory T cells in autoimmune diseases
Cvetanovich GL, Hafler DA. Human regulatory T cells in autoimmune diseases. Current Opinion In Immunology 2010, 22: 753-760. PMID: 20869862, PMCID: PMC2997859, DOI: 10.1016/j.coi.2010.08.012.Peer-Reviewed Original Research
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
2008
Human regulatory T cells and autoimmunity
Costantino CM, Baecher‐Allan C, Hafler DA. Human regulatory T cells and autoimmunity. European Journal Of Immunology 2008, 38: 921-924. PMID: 18395861, PMCID: PMC2752283, DOI: 10.1002/eji.200738104.Peer-Reviewed Original Research