2022
RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice.
Joshi AA, Wu Y, Deng S, Preston-Hurlburt P, Forbes JM, Herold KC. RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice. Clinical Immunology 2022, 245: 109165. PMID: 36257528, DOI: 10.1016/j.clim.2022.109165.Peer-Reviewed Original ResearchConceptsXenograft rejectionIL-17AHumanized miceIL-1βT cellsImmune responseRAGE antagonistsAdaptive human immune responsesPD-1 expressionSkin graft rejectionHuman immune cell responsesImmune cell responsesHuman immune responseHuman immune cellsInnate immune responseAdvanced glycation endproductsInhibition of pathwaysSmall molecule antagonistsMultiple inflammatory processesAZ therapyRAGE antagonismGraft rejectionIL-23Serum levelsMedian time
2017
Microbiota control immune regulation in humanized mice
GĂĽlden E, Vudattu NK, Deng S, Preston-Hurlburt P, Mamula M, Reed JC, Mohandas S, Herold BC, Torres R, Vieira SM, Lim B, Herazo-Maya JD, Kriegel M, Goodman AL, Cotsapas C, Herold KC. Microbiota control immune regulation in humanized mice. JCI Insight 2017, 2: e91709. PMID: 29093268, PMCID: PMC5752290, DOI: 10.1172/jci.insight.91709.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, AntinuclearAntibodies, Monoclonal, HumanizedAutoimmune DiseasesB7-2 AntigenCD11b AntigenCD11c AntigenCD3 ComplexCD8-Positive T-LymphocytesCytokinesDisease Models, AnimalGastrointestinal MicrobiomeGastrointestinal TractGraft RejectionHumansImmunosuppressive AgentsImmunotherapyInterferon-gammaInterleukin-10Interleukin-27Leukocytes, MononuclearMiceMice, KnockoutMucous MembraneSkin TransplantationSTAT5 Transcription FactorT-LymphocytesTransplantation, HeterologousConceptsT cellsIL-10Humanized miceHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsIL-27 expressionIL-10 levelsAnti-nuclear antibodiesEffector T cellsLevels of IFNCentral memory cellsLess IL-10Markers of efficacyBlood mononuclear cellsExpression of CD86Immune regulatory pathwaysIL-10 inductionHuman immune cellsHuman stool samplesImmunosuppressive medicationsIL-27Xenograft rejectionImmune therapyMononuclear cellsAntibiotic treatmentOral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice
Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clinical Immunology 2017, 183: 240-246. PMID: 28739191, DOI: 10.1016/j.clim.2017.07.005.Peer-Reviewed Original ResearchConceptsSkin xenograft rejectionOral treatmentXenograft rejectionT cellsAnti-CD3 monoclonal antibodyConsecutive daily dosesPeripheral T cellsActivation of splenocytesHuman immune systemSplenic CD8Graft acceptanceWeekly dosingIL-10Serum levelsImmune therapySmall bowelHumanized miceDaily dosesImmune modulationMucosal barrierIntragastric doseOral administrationSkin graftsProliferative responseLymphoid cells
2016
Pillars Article: Sequence Analysis of Peptides Bound to MHC Class II Molecules. Nature. 1991. 353: 622-627.
Rudensky A, Preston-Hurlburt P, Hong S, Barlow A, Janeway C. Pillars Article: Sequence Analysis of Peptides Bound to MHC Class II Molecules. Nature. 1991. 353: 622-627. The Journal Of Immunology 2016, 196: 941-6. PMID: 26802059, DOI: 10.1093/jimmunol/196.3.941.Peer-Reviewed Original Research
2014
Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy
Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, Raycroft MT, Mamula MJ, Herold KC. Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy. The Journal Of Immunology 2014, 193: 587-596. PMID: 24943216, PMCID: PMC4123131, DOI: 10.4049/jimmunol.1302455.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal GlandsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAutoimmune DiseasesCytokinesDisease Models, AnimalFlow CytometryHumansInterleukin Receptor Common gamma SubunitIpilimumabLiverLymphocyte ActivationMacrophagesMiceMice, Inbred NODMice, KnockoutMice, SCIDPhosphorylationSTAT5 Transcription FactorStem Cell TransplantationSurvival AnalysisT-LymphocytesT-Lymphocytes, RegulatoryTransplantation, HeterologousWeight LossConceptsAnti-nuclear AbsAutoimmune diseasesRegulatory cellsHumanized miceT cellsImmune responseWeight lossMesenteric lymph nodesHuman autoimmune diseasesInduction of autoimmunityT-cell immunotherapyRelease of IFNHuman immune responseImmune-deficient miceIpilimumab treatmentInflammatory sequelaeLymph nodesCell immunotherapyIP-10Macrophage infiltrationCytokine productionSpleen cellsPathologic processesHepatitisMiceThe Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma
Akirav EM, Henegariu O, Preston-Hurlburt P, Schmidt AM, Clynes R, Herold KC. The Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma. PLOS ONE 2014, 9: e95678. PMID: 24759895, PMCID: PMC3997417, DOI: 10.1371/journal.pone.0095678.Peer-Reviewed Original ResearchConceptsAdaptive immune responsesT cell responsesEffects of RAGEGlycation end productsT cell activationT cellsImmune responseWT miceCellular infiltrationCell activationCell responsesBronchial alveolar lavage fluidAdvanced glycation end productsMediastinal lymph nodesT cell infiltrationIL-5 productionOT-II miceRAGE-deficient miceT cell subsetsAlveolar lavage fluidMultiplex bead analysisRole of RAGET cell proliferationDeficient T cellsT cell differentiation
2012
Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice
Waldron-Lynch F, Deng S, Preston-Hurlburt P, Henegariu O, Herold KC. Analysis of Human Biologics With a Mouse Skin Transplant Model in Humanized Mice. American Journal Of Transplantation 2012, 12: 2652-2662. PMID: 22900715, DOI: 10.1111/j.1600-6143.2012.04178.x.Peer-Reviewed Original ResearchConceptsSkin transplant modelGraft rejectionTransplant modelHumanized miceSkin graftsT cellsFunctional human immune responsesMouse skin transplant modelMurine skin transplant modelCentral memory T cellsNOD/SCID/Mouse skin graftsMemory T cellsMonoclonal antibody therapySkin graft rejectionDevelopment of effectorHuman immune responseMHC class IHuman T cellsIpilimumab treatmentAntibody therapySCID/Diffuse infiltrationMouse donorsSerum immunoglobulinsEnhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes
Czyzyk J, Henegariu O, Preston-Hurlburt P, Baldzizhar R, Fedorchuk C, Esplugues E, Bottomly K, Gorus FK, Herold K, Flavell RA. Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes. The Journal Of Immunology 2012, 188: 6319-6327. PMID: 22593614, PMCID: PMC3370061, DOI: 10.4049/jimmunol.1200467.Peer-Reviewed Original ResearchConceptsAutoimmune diabetes-prone NOD miceDiabetes-prone NOD miceHuman type 1 diabetesAnti-insulin autoantibodiesOnset of diabetesProtective humoral immunityType 1 diabetesNOD miceAutoimmune inflammationIslet inflammationNOD modelSuboptimal doseAutoimmune diseasesHumoral immunityImmunological toleranceT cellsHumoral activityType 1Early onsetDiabetesElevated levelsClade B serpinsAutoantibodiesInflammationProtease inhibitorsTeplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells
2011
Synergistic Reversal of Type 1 Diabetes in NOD Mice With Anti-CD3 and Interleukin-1 Blockade Evidence of Improved Immune Regulation
Ablamunits V, Henegariu O, Hansen JB, Opare-Addo L, Preston-Hurlburt P, Santamaria P, Mandrup-Poulsen T, Herold KC. Synergistic Reversal of Type 1 Diabetes in NOD Mice With Anti-CD3 and Interleukin-1 Blockade Evidence of Improved Immune Regulation. Diabetes 2011, 61: 145-154. PMID: 22043003, PMCID: PMC3237664, DOI: 10.2337/db11-1033.Peer-Reviewed Original ResearchConceptsReversal of diabetesNOD miceIL-1raIL-1βIL-1 receptor antagonistAnti-CD3 monoclonal antibodyCombination-treated miceIgG1 isotype antibodiesPancreatic lymph nodesMore IL-10Hyperglycemic NOD miceType 1 diabetesEffect of treatmentIntrapancreatic expressionSynergistic reversalAutoimmune diabetesIsotype antibodiesAdoptive transferIL-17Dendritic cellsIL-10Lymph nodesPersistent remissionIslet inflammationIL-6TH17 cells mediate pulmonary collateral priming
Albrecht M, Chen HC, Preston-Hurlburt P, Ranney P, Hoymann HG, Maxeiner J, Staudt V, Taube C, Bottomly HK, Dittrich AM. TH17 cells mediate pulmonary collateral priming. Journal Of Allergy And Clinical Immunology 2011, 128: 168-177.e8. PMID: 21459426, PMCID: PMC3129446, DOI: 10.1016/j.jaci.2011.01.067.Peer-Reviewed Original ResearchConceptsCollateral primingAirway inflammationNew antigensAirway hyperresponsivenessIL-17AT cellsMemory/effector phenotypeCognate antigenLymphocytic airway inflammationStronger airway hyperresponsivenessIL-17A secretionEndogenous T cellsAirway responsivenessIgG2a levelsOngoing inflammationTh17 cellsAllergic sensitizationLymphocytic inflammationEffector phenotypePulmonary inflammationInflammatory phenotypeUnrelated antigensMurine modelInflammationCongenic mice
2008
A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development
Jani A, Wan M, Zhang J, Cui K, Wu J, Preston-Hurlburt P, Khatri R, Zhao K, Chi T. A novel genetic strategy reveals unexpected roles of the Swi–Snf–like chromatin-remodeling BAF complex in thymocyte development. Journal Of Experimental Medicine 2008, 205: 2813-2825. PMID: 18955569, PMCID: PMC2585832, DOI: 10.1084/jem.20080938.Peer-Reviewed Original ResearchConceptsPoint mutantsUnexpected roleImportant gene functionsThymocyte developmentNovel genetic strategyPoint mutationsEarly thymocyte developmentMammalian geneticsChromatin templatesSWI-SNFBAF complexGene functionATPase subunitsDeletion mutantsFactor complexCD4 locusTarget genesGenetic strategiesCD4 activationMutantsNovel activityPhysical interactionDeletionBRGMutations
2002
Dual receptor T cells extend the immune repertoire for foreign antigens
He X, Janeway CA, Levine M, Robinson E, Preston-Hurlburt P, Viret C, Bottomly K. Dual receptor T cells extend the immune repertoire for foreign antigens. Nature Immunology 2002, 3: 127-134. PMID: 11812989, DOI: 10.1038/ni751.Peer-Reviewed Original ResearchConceptsDual TCR cellsT cell receptorTCR cellsForeign antigensT cellsDual-receptor T cellsFunctional T cell receptorSecond T cell receptorReceptor T cellsAutoimmune potentialIntrathymic selectionTCR repertoireNormal miceImmune responseImmune systemCell receptorNaĂŻve repertoireAntigenClonal expansionImmune repertoireBeneficial roleCellsMost studiesMiceReceptors
1998
MyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways
Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway C. MyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways. Molecular Cell 1998, 2: 253-258. PMID: 9734363, DOI: 10.1016/s1097-2765(00)80136-7.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationDrosophilaDrosophila ProteinsHumansInterleukin-1 Receptor-Associated KinasesMembrane GlycoproteinsMembrane ProteinsMyeloid Differentiation Factor 88NF-kappa BProtein KinasesProteinsReceptors, Cell SurfaceReceptors, ImmunologicReceptors, Interleukin-1Signal TransductionTNF Receptor-Associated Factor 6Toll-Like ReceptorsTranscription Factor AP-1ConceptsIL-1R familyNF-kappaB activationNF-kappaB pathwayImmune response genesToll/IL-1R familyAP-1 activationImmune responseIL-1RTRAF6 proteinInnate immunityNF-kappaBMyD88Drosophila Toll proteinReceptor familyToll receptorAdaptor proteinSignaling pathwaysReceptorsActivationToll proteinRegulator moleculesResponse genesAdult DrosophilaPathwayProtein
1997
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov R, Preston-Hurlburt P, Janeway C. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388: 394-397. PMID: 9237759, DOI: 10.1038/41131.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenCell LineCloning, MolecularDrosophilaDrosophila ProteinsHumansImmunityInsect ProteinsInterleukinsJurkat CellsMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataMutationNF-kappa BReceptors, Cell SurfaceReceptors, ImmunologicRecombinant Fusion ProteinsSequence Homology, Amino AcidSignal TransductionT-LymphocytesToll-Like ReceptorsTransfectionConceptsDrosophila Toll proteinToll proteinCytoplasmic domainDrosophila TollHuman homologueLeucine-rich repeat domainNF-ÎşB-controlled genesHuman cell linesRepeat domainActive mutantExtracellular domainNF-ÎşBImmune responseInnate immune responseCo-stimulatory molecules B7.1Adaptive immune systemComponents of immunityInflammatory cytokines IL-1ProteinCell linesCo-stimulatory moleculesAntigen-presenting cellsAdaptive immune responsesNaive T cellsHomologues
1996
The Specificity and Orientation of a TCR to its Peptide–MHC Class II Ligands
Sant'Angelo D, Waterbury G, Preston-Hurlburt P, Yoon S, Medzhitov R, Hong S, Janeway C. The Specificity and Orientation of a TCR to its Peptide–MHC Class II Ligands. Immunity 1996, 4: 367-376. PMID: 8612131, DOI: 10.1016/s1074-7613(00)80250-2.Peer-Reviewed Original Research
1992
Truncation variants of peptides isolated from MHC class II molecules suggest sequence motifs
Rudensky A, Preston-Hurlburt, P, Al-Ramadi B, Rothbard J, Janeway C. Truncation variants of peptides isolated from MHC class II molecules suggest sequence motifs. Nature 1992, 359: 429-431. PMID: 1328884, DOI: 10.1038/359429a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen-Antibody ReactionsBacterial ProteinsBinding Sites, AntibodyCell LineChromatography, High Pressure LiquidHistocompatibility Antigens Class IIImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMolecular Sequence DataPeptide FragmentsReceptors, TransferrinRepressor ProteinsSequence AlignmentSequence Homology, Amino AcidT-LymphocytesViral Envelope ProteinsConceptsMHC class II moleculesClass II moleculesMHC class IMajor histocompatibility complexCD4 T cell recognitionClass IForeign protein antigensMHC class IIT cell recognitionT cellsMHC moleculesClass IIProtein antigensHistocompatibility complexAntigenic peptidesOuter aspectPeptide-binding cleftAmino acid differencesAnchor residuesAllelic variantsSingle peptide sequenceDifferent allelic formsPeptidesTruncation variantsAllelic forms
1991
Sequence analysis of peptides bound to MHC class II molecules
Rudensky A, Preston-Hurlburt P, Hong S, Barlow A, Janeway C. Sequence analysis of peptides bound to MHC class II molecules. Nature 1991, 353: 622-627. PMID: 1656276, DOI: 10.1038/353622a0.Peer-Reviewed Original ResearchOn the complexity of self
Rudensky A, Rath S, Preston-Hurlburt P, Murphy D, Janeway C. On the complexity of self. Nature 1991, 353: 660-662. PMID: 1656278, DOI: 10.1038/353660a0.Peer-Reviewed Original ResearchConceptsMHC class II moleculesClass II moleculesSelf peptidesT cellsY-AeSelf MHC class II moleculesCD4 T cellsMajor histocompatibility complex moleculesMHC class IIMHC class II complexesHistocompatibility complex moleculesClass II complexesIntrathymic selectionSelf antigensIntrathymic developmentNovel MHCClass II
1990
The role of tyrosine at the ligand-binding site of the nicotinic acetylcholine receptor
Pearce S, Preston-Hurlburt P, Hawrot E. The role of tyrosine at the ligand-binding site of the nicotinic acetylcholine receptor. Proceedings Of The Royal Society B 1990, 241: 207-213. PMID: 1979446, DOI: 10.1098/rspb.1990.0087.Peer-Reviewed Original ResearchConceptsLigand-binding siteNegative subsiteInvariant tyrosine residueNicotinic acetylcholine receptorsValuable structural informationDetailed structural knowledgeReceptor ligand-binding siteCationic ligandsFluorescence spectroscopicAcetylcholine receptorsRole of tyrosineCritical residuesLigand recognitionTyrosine residuesLigand bindingStructural comparisonStructural informationPeptide fragmentsLigandsPosition 190Receptor actionNeurotransmitter receptorsSpecific ligandsStructural knowledgeResidues
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