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
2016
Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells
Arterbery AS, Osafo-Addo A, Avitzur Y, Ciarleglio M, Deng Y, Lobritto SJ, Martinez M, Hafler DA, Kleinewietfeld M, Ekong UD. Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells. The Journal Of Immunology 2016, 196: 4040-4051. PMID: 27183637, PMCID: PMC4874532, DOI: 10.4049/jimmunol.1502276.Peer-Reviewed Original ResearchConceptsRegulatory T cellsIL-12IL-6T cellsSuppressive functionDe novo autoimmune hepatitisHuman regulatory T cellsNovo autoimmune hepatitisProinflammatory IL-12Th17 effector cellsTregs of patientsDifferentiation of TregsIL-17 cytokinesBlockade of IFNMonocyte/macrophage cellsLiver of subjectsAutoimmune hepatitisDominant cytokineProinflammatory IFNTH1-likeIL-17Treg phenotypeTreg dysfunctionEffector cellsInflammatory milieu
2013
The 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 approaches
2011
An Innate Role for IL-17
Dominguez-Villar M, Hafler DA. An Innate Role for IL-17. Science 2011, 332: 47-48. PMID: 21454778, DOI: 10.1126/science.1205311.Peer-Reviewed Original ResearchConceptsImmune responseImmune dysregulation polyendocrinopathyAbnormal immune responseRegulatory immune cellsRegulatory T cellsHuman autoimmune disordersCytokine interleukin-17Normal immune responseTranscription factor Foxp3IL-17Interleukin-17Autoimmune disordersAutoimmune diseasesImmune cellsImmune system processFOXP3 geneFactor Foxp3T cellsImmune systemFungal infectionsGenetic mutationsHuman genetic mutationsCytokinesInfectionCell typesCD2 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 ResearchTGF-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 ResearchIL-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
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