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
2021
The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity
Kuchroo JR, Hafler DA, Sharpe AH, Lucca LE. The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity. Science Immunology 2021, 6: eabf4034. PMID: 34739340, DOI: 10.1126/sciimmunol.abf4034.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsPD-1 blockadeRegulatory T cell functionImmune checkpoint blockadeCheckpoint blockade immunotherapyT cell responsesT cell functionBlockade immunotherapyAdverse eventsAntitumor immunityCheckpoint blockadeCell responsesBlockadeCell functionAutoimmunityMechanistic featuresEdged swordImmunotherapyTumorsCancerImmunity
2020
Epigenetic fine-mapping: identification of causal mechanisms for autoimmunity
Lincoln MR, Axisa PP, Hafler DA. Epigenetic fine-mapping: identification of causal mechanisms for autoimmunity. Current Opinion In Immunology 2020, 67: 50-56. PMID: 32977183, DOI: 10.1016/j.coi.2020.09.002.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMolecular mechanismsSusceptibility lociIndividual susceptibility lociFundamental genetic basisCausal molecular mechanismsPathogenic cell typesSpecific molecular mechanismsGenetic susceptibility lociEpigenetic techniquesGenetic basisGenetic lociAssociation studiesCell typesLociRecent advancesMechanismGeneticsAutoimmune diseasesSpectrum of autoimmunityCausal mechanismsEtiological mechanismsInflammatory diseasesTranslationAutoimmunity
2019
Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients
James JA, Chen H, Young KA, Bemis EA, Seifert J, Bourn RL, Deane KD, Demoruelle MK, Feser M, O'Dell JR, Weisman MH, Keating RM, Gaffney PM, Kelly JA, Langefeld CD, Harley JB, Robinson W, Hafler DA, O'Connor KC, Buckner J, Guthridge JM, Norris JM, Holers VM. Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients. EBioMedicine 2019, 42: 76-85. PMID: 30952617, PMCID: PMC6491794, DOI: 10.1016/j.ebiom.2019.03.063.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusFirst-degree relativesGenetic risk scoreRA patientsRheumatoid arthritisSLE patientsT1D patientsAutoantibody-positive systemic lupus erythematosusRisk first-degree relativesOrgan-specific autoimmune diseasesType 1 diabetes patientsAutoimmune disease preventionAnti-tissue transglutaminaseDisease-associated autoantibodiesDisease prevention studiesUnaffected first-degree relativesCross-sectional studyLatent autoimmunityLupus erythematosusAutoimmune diseasesDiabetes patientsPrevention StudyRisk scoreAutoimmunityPreclinical periodCHAPTER 2 Genetics of Multiple Sclerosis
Abulaban A, Hafler D, Longbrake E. CHAPTER 2 Genetics of Multiple Sclerosis. 2019, 33-54. DOI: 10.1039/9781788016070-00033.ChaptersMultiple sclerosisCentral nervous systemImmune cell infiltratesComplex autoimmune diseaseEnvironmental risk factorsExtensive CNS demyelinationMS therapyAxonal damageCell infiltrateCNS demyelinationAutoimmune diseasesRisk factorsGenetic predispositionNervous systemDisease severityDiseaseSclerosisComplex genetic diseasesChapter 2 GeneticsGenetic diseasesDemyelinationInfiltratesAutoimmunityPathogenesisTherapy
2018
Regulatory 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
2015
Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells
Hernandez AL, Kitz A, Wu C, Lowther DE, Rodriguez DM, Vudattu N, Deng S, Herold KC, Kuchroo VK, Kleinewietfeld M, Hafler DA. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. Journal Of Clinical Investigation 2015, 125: 4212-4222. PMID: 26524592, PMCID: PMC4639983, DOI: 10.1172/jci81151.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, NeutralizingAutoimmunityCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesColitisCytokinesForkhead Transcription FactorsGene Expression ProfilingGenes, ReporterGraft vs Host DiseaseHeterograftsHumansImmediate-Early ProteinsInflammationInterferon-gammaLeukocytes, MononuclearMaleMiceProtein Serine-Threonine KinasesRNA InterferenceRNA, Small InterferingSodium ChlorideSodium Chloride, DietaryT-Lymphocytes, RegulatoryConceptsHigh-salt dietTreg functionIFNγ secretionCD4 effector cellsHuman Treg functionRegulatory T cellsAdoptive transfer modelAnti-IFNγ antibodyHost disease modelType 1 diabetesInduction of proinflammatoryTreg pathwayExperimental colitisXenogeneic graftEffector cellsMultiple sclerosisProinflammatory responseT cellsTregsMurine modelSuppressive activitySuppressive functionSerum/glucocorticoid-regulated kinaseAutoimmunityGlucocorticoid-regulated kinaseThe TIGIT/CD226/CD155 axis is differentially expressed in MS and glioblastoma: implications for autoimmunity and tumor immune escape. (P4.043)
Lowther D, Ramanan S, DeBartolo D, Park C, Duan X, Hafler D, Pitt D. The TIGIT/CD226/CD155 axis is differentially expressed in MS and glioblastoma: implications for autoimmunity and tumor immune escape. (P4.043). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.p4.043.Peer-Reviewed Original Research
2013
Role of “Western Diet” in Inflammatory Autoimmune Diseases
Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Current Allergy And Asthma Reports 2013, 14: 404. PMID: 24338487, PMCID: PMC4034518, DOI: 10.1007/s11882-013-0404-6.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesWestern dietInflammatory autoimmune diseaseExcess salt intakeImmunologic mechanismsMetabolic syndromeSalt intakeAutoimmune pathologyCardiovascular diseaseT cellsWesternized countriesFrequent consumptionDietary influencesInfectious diseasesDiseaseNutritional patternsFast foodPathogen exposureDietCurrent knowledgeCentral playerAutoimmunityObesitySyndromeCholesterol
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 ResearchRegulation of Immunological Tolerance and Autoimmunity by the Enzyme Sialic Acid Acetylesterase (SIAE)
Surolia I, Pirnie S, Chellappa V, Annaiah C, Moya J, Bell D, Haider K, Taylor K, De Jager P, Behrens T, Hafler D, Sands B, Murali M, Gregersen P, Pillai S. Regulation of Immunological Tolerance and Autoimmunity by the Enzyme Sialic Acid Acetylesterase (SIAE). Clinical Immunology 2010, 135: s16. DOI: 10.1016/j.clim.2010.03.054.Peer-Reviewed Original Research
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
2006
The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells
Baecher-Allan C, Hafler DA. The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells. Current Protocols In Immunology 2006, 72: 7.4b.1-7.4b.12. PMID: 18432975, DOI: 10.1002/0471142735.im0704bs72.Peer-Reviewed Original ResearchConceptsRegulatory T cellsCD4 T cellsT cellsHuman regulatory T cellsHuman CD4 T cellsLevels of CD25Suppressive featuresCD25Coculture assaysVitro proliferationHigh expressionVivo developmentEndogenous expressionSuch cellsCellsSmall percentageMouse cellsHigh levelsAutoimmunityHumansExpressionMiceBlood
1999
The B7–CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system
Anderson D, Sharpe A, Hafler D. The B7–CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Current Opinion In Immunology 1999, 11: 677-683. PMID: 10631554, DOI: 10.1016/s0952-7915(99)00036-9.Peer-Reviewed Original ResearchConceptsSelf-reactive T cellsB7-CD28/CTLAAutoimmune diseasesT cellsTh1/Th2 cell differentiationB7-CD28 costimulationHuman autoimmune diseasesCentral nervous systemTh2 cell differentiationCostimulatory pathwayEffector phaseCTLA-4Nervous systemCritical roleDiseaseCTLARecent studiesCell differentiationCellsPast yearPathwayAutoimmunityCD28InitiationCostimulation
1998
T helper cell differentiation in multiple sclerosis and autoimmunity
Martin R, Ruddle N, Reingold S, Hafler D. T helper cell differentiation in multiple sclerosis and autoimmunity. Trends In Immunology 1998, 19: 495-498. PMID: 9818541, DOI: 10.1016/s0167-5699(98)01345-0.Peer-Reviewed Original Research