2015
A Dendritic-Cell-Stromal Axis Maintains Immune Responses in Lymph Nodes
Kumar V, Dasoveanu DC, Chyou S, Tzeng TC, Rozo C, Liang Y, Stohl W, Fu YX, Ruddle NH, Lu TT. A Dendritic-Cell-Stromal Axis Maintains Immune Responses in Lymph Nodes. Immunity 2015, 42: 719-730. PMID: 25902483, PMCID: PMC4591553, DOI: 10.1016/j.immuni.2015.03.015.Peer-Reviewed Original ResearchConceptsDendritic cellsImmune responseReticular cellsLymph nodesFunction of DCsOngoing immune responseCell survivalSecondary lymphoid tissuesBeta-receptor ligandsStromal reticular cellsPathogenic lymphocytesLymphoproliferative diseaseLymphocyte functionLymphoid tissueLymphocyte survivalCritical mediatorPodoplaninReceptor ligandsCell functionSurvivalLTβRDiseasePotential strategyCellsResponse
2013
Lymphatic Vessel Function in Head and Neck Inflammation
Truman LA, A-Gonzalez N, Bentley KL, Ruddle NH. Lymphatic Vessel Function in Head and Neck Inflammation. Lymphatic Research And Biology 2013, 11: 187-192. PMID: 24044758, PMCID: PMC3780307, DOI: 10.1089/lrb.2013.0013.Peer-Reviewed Original ResearchConceptsIndividual lymphatic endothelial cellsLymphatic endothelial cellsRed fluorescent reporterEndothelial cellsLymphatic vesselsTranscription factorsRegulatory elementsFaithful expressionProx1 expressionLymphatic vessel functionSingle cellsReporter miceLymphangiogenesisTd-TomatoJackson LaboratoryCellsVivoTdTomatoExpressionProx1TransgeneReporterImmune responseVessel functionMice
2012
Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
Kuerten S, Schickel A, Kerkloh C, Recks MS, Addicks K, Ruddle NH, Lehmann PV. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response. Acta Neuropathologica 2012, 124: 861-873. PMID: 22842876, DOI: 10.1007/s00401-012-1023-3.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsExperimental autoimmune encephalomyelitisMyelin-specific T cell responseCentral nervous systemB cell aggregatesT cell responsesMultiple sclerosisB cell aggregationDeterminant spreadingB cellsCell responsesActive immune responseMyelin basic proteinLymphoid neogenesisAutoimmune encephalomyelitisMS patientsAggressive diseaseAutoimmune pathologyPatient populationLymphoid organsDisease onsetDisease progressionT cellsImmune responsePathogenic contributionA Switch in Pathogenic Mechanism in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in IFN-γ–Inducible Lysosomal Thiol Reductase-Free Mice
Bergman CM, Marta CB, Maric M, Pfeiffer SE, Cresswell P, Ruddle NH. A Switch in Pathogenic Mechanism in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in IFN-γ–Inducible Lysosomal Thiol Reductase-Free Mice. The Journal Of Immunology 2012, 188: 6001-6009. PMID: 22586035, PMCID: PMC4133136, DOI: 10.4049/jimmunol.1101898.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen-Presenting CellsEncephalomyelitis, Autoimmune, ExperimentalFluorescent Antibody TechniqueGlycoproteinsHumansImmunoblottingMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMyelin ProteinsMyelin-Oligodendrocyte GlycoproteinOxidoreductasesOxidoreductases Acting on Sulfur Group DonorsPeptide FragmentsRatsSequence Homology, Amino AcidProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets
Truman LA, Bentley KL, Smith EC, Massaro SA, Gonzalez DG, Haberman AM, Hill M, Jones D, Min W, Krause DS, Ruddle NH. ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets. American Journal Of Pathology 2012, 180: 1715-1725. PMID: 22310467, PMCID: PMC3349900, DOI: 10.1016/j.ajpath.2011.12.026.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal MedullaAnimalsBlood PlateletsCells, CulturedCytoplasmEndothelial CellsGene Expression RegulationGenotypeGlycoproteinsHomeodomain ProteinsLuminescent ProteinsLymph NodesLymphatic VesselsMegakaryocytesMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMicroscopy, FluorescenceTumor Cells, CulturedTumor Suppressor ProteinsConceptsLymph nodesLymphatic vesselsAdrenal medullaExpression of Prox1Tumor metastasisHigh endothelial venulesProx1 expressionTwo-photon laser scanning microscopyTransplant rejectionDentate gyrusEndothelial venulesAntigen presentationC57BL/6 backgroundTransgenic miceLipid metabolismMiceNeuroendocrine cellsAdult liverNovel siteMetastasisMedullaStudy of diseasesLiving mouseUnknown rolePotential utility
2011
Impaired lymphatic contraction associated with immunosuppression
Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP. Impaired lymphatic contraction associated with immunosuppression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 18784-18789. PMID: 22065738, PMCID: PMC3219138, DOI: 10.1073/pnas.1116152108.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseLymphatic contractionsLymphatic functionImmune responseAntigen-presenting cellsNitric oxide synthaseEffective immune responseUnique mouse modelLymphatic vessel contractionLymphatic vessel functionLymph nodesAutoreactive responsesMultiple sclerosisVessel contractionInflammatory conditionsInducible NOSOxide synthaseMouse modelLymphatic metastasisVessel functionLymphatic endothelial cellsNitric oxideEndothelial cellsIntravital imagingPotential mechanismsBlocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses
Motallebzadeh R, Rehakova S, Conlon TM, Win TS, Callaghan CJ, Goddard M, Bolton EM, Ruddle NH, Bradley JA, Pettigrew GJ. Blocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses. The FASEB Journal 2011, 26: 51-62. PMID: 21926237, DOI: 10.1096/fj.11-186973.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBone MarrowCD4-Positive T-LymphocytesChoristomaChronic DiseaseGraft RejectionHeart TransplantationIsoantibodiesLymphoid TissueLymphotoxin beta ReceptorLymphotoxin-betaMiceMice, Inbred C57BLMice, KnockoutMyocardiumNeovascularization, PathologicRecombinant Fusion ProteinsSignal TransductionSpleenTransplantation, HomologousConceptsTertiary lymphoid organsCardiac allograftsHeart allograftsB cellsLymphotoxin β receptor (LTβR) signalingEctopic lymphoid tissueGerminal center activityLTβR-IgTLO formationPostoperative administrationAccelerated rejectionHumoral autoimmunityAlloimmune responseAutoantibody productionAutoantibody responseHumoral responseLymphoid organsLymphoid tissueLymphoid organogenesisEffector antibodiesMouse modelAllograftsTransplantationAutoantibodiesCellsResident B cells regulate thymic expression of myelin oligodendrocyte glycoprotein
Akirav EM, Xu Y, Ruddle NH. Resident B cells regulate thymic expression of myelin oligodendrocyte glycoprotein. Journal Of Neuroimmunology 2011, 235: 33-39. PMID: 21550671, PMCID: PMC3157307, DOI: 10.1016/j.jneuroim.2011.03.013.Peer-Reviewed Original ResearchConceptsB cellsB cell-deficient μMT miceMyelin oligodendrocyte glycoproteinResident B cellsThymic B cellsCortico-medullary junctionMinor cell populationProduction of LTInsulin mRNA expressionΜMT miceEpithelial cell numberOligodendrocyte glycoproteinThymic expressionAntigen expressionMRNA expressionNormal tissuesCell populationsCell numberCellsExpressionLtUnexpected roleBiological roleLymphotoxinMice
2009
Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens
Akirav EM, Bergman CM, Hill M, Ruddle NH. Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens. Journal Of Neuroscience Research 2009, 87: 3511-3519. PMID: 19125411, PMCID: PMC4429897, DOI: 10.1002/jnr.21981.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAutoantigensAutoimmunityBiomarkersCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCentral Nervous SystemChemotaxis, LeukocyteDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleInterferon-gammaInterleukin-10Interleukin-17Interleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred C57BLMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinAutoimmune encephalomyelitisT cellsIL-10-producing cellsRegulatory T cellsTissue-restricted antigensCentral nervous systemField of autoimmunityT cell activationTreg depletionEAE severitySelf antigensOligodendrocyte glycoproteinForeign antigensExperimental diseaseNervous systemRelated antigensMiceSelf-antigen specificityAntigenTregsEncephalomyelitisAutoimmunityRats
2007
Dynamic Imaging of Lymphatic Vessels and Lymph Nodes Using a Bimodal Nanoparticulate Contrast Agent
Mounzer R, Shkarin P, Papademetris X, Constable T, Ruddle NH, Fahmy TM. Dynamic Imaging of Lymphatic Vessels and Lymph Nodes Using a Bimodal Nanoparticulate Contrast Agent. Lymphatic Research And Biology 2007, 5: 151-158. PMID: 18035933, DOI: 10.1089/lrb.2007.5302.Peer-Reviewed Original ResearchTransgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules
Liao S, Bentley K, Lebrun M, Lesslauer W, Ruddle FH, Ruddle NH. Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 4577-4582. PMID: 17360566, PMCID: PMC1838643, DOI: 10.1073/pnas.0700334104.Peer-Reviewed Original ResearchConceptsDNA fragmentsTertiary lymphoid organsExpression of reporterEndogenous gene expressionBAC DNA fragmentsTissue-specific expressionBeta-galactosidase reporter geneHomologous recombination techniquesLymphoid organsLymphoid tissueEffector genesBAC clonesEndogenous genesRegulatory sequencesNasal-associated lymphoid tissueReporter geneGene expressionLacZ constructLTbetaR-Ig treatmentExon IIHEV-like vesselsGenesHigh endothelial venulesMolecular natureRecombination techniquesTertiary Lymphoid Tissues Generate Effector and Memory T Cells That Lead to Allograft Rejection
Nasr IW, Reel M, Oberbarnscheidt MH, Mounzer RH, Baddoura FK, Ruddle NH, Lakkis FG. Tertiary Lymphoid Tissues Generate Effector and Memory T Cells That Lead to Allograft Rejection. American Journal Of Transplantation 2007, 7: 1071-1079. PMID: 17359505, DOI: 10.1111/j.1600-6143.2007.01756.x.Peer-Reviewed Original ResearchConceptsTertiary lymphoid tissueWild-type allograftsMemory T cellsSecondary lymphoid organsLymphoid tissueT cellsLymphoid organsRejection processPrimary alloimmune responsesSyngeneic graft recipientsMemory immune responsesNaïve T cell activationTertiary lymphoid structuresNaive T cellsT cell activationMurine transplantation modelChronic rejectionAllograft rejectionGraft recipientsAlloimmune responseLymphoid structuresChronic inflammationSkin allograftsNaïve lymphocytesTransplantation model
2006
Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid
Marinkovic T, Garin A, Yokota Y, Fu YX, Ruddle NH, Furtado GC, Lira SA. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. Journal Of Clinical Investigation 2006, 116: 2622-2632. PMID: 16998590, PMCID: PMC1570377, DOI: 10.1172/jci28993.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCell Adhesion MoleculesCell CommunicationCell MovementChemokine CCL21ChemokinesChemokines, CCDendritic CellsDNA-Binding ProteinsGene ExpressionGreen Fluorescent ProteinsInhibitor of Differentiation Protein 2Lymphoid TissueLymphotoxin-alphaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, CCR7Receptors, ChemokineThyroid DiseasesThyroid GlandSynchrony of High Endothelial Venules and Lymphatic Vessels Revealed by Immunization
Liao S, Ruddle NH. Synchrony of High Endothelial Venules and Lymphatic Vessels Revealed by Immunization. The Journal Of Immunology 2006, 177: 3369-3379. PMID: 16920978, DOI: 10.4049/jimmunol.177.5.3369.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersB-LymphocytesCell Adhesion MoleculesCell CommunicationCells, CulturedDendritic CellsDown-RegulationEndotheliumImmunizationLymphangiogenesisLymphatic VesselsLymphotoxin beta ReceptorMiceMice, Inbred C57BLMice, KnockoutMucoproteinsOxazolonePhenotypeReceptors, Tumor Necrosis FactorTime FactorsT-LymphocytesVenulesConceptsHigh endothelial venulesB cellsEndothelial venulesPLN high endothelial venulesPeripheral lymph node high endothelial venulesLymph node high endothelial venulesMature phenotypeLTbetaR-Ig treatmentT cell primingLYVE-1Evans blue dyeLymphotoxin beta receptorLTbetaR-IgCell primingLV functionOVA immunizationImmature phenotypeDay 7Day 4Functional insufficiencyImmunizationClose physical contactLVRemodeling processLymphatic vessels
2005
Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology
Marta CB, Oliver AR, Sweet RA, Pfeiffer SE, Ruddle NH. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13992-13997. PMID: 16172404, PMCID: PMC1236555, DOI: 10.1073/pnas.0504979102.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAutoantibodiesB-LymphocytesEncephalomyelitis, Autoimmune, ExperimentalGlycosylationHumansImmunizationImmunodominant EpitopesImmunoglobulin GMiceMice, Inbred C57BLMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinOligodendrogliaProlineRatsSerineConceptsHuman myelin oligodendrocyte glycoproteinMyelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisAnti-MOG antibodiesMultiple sclerosis patientsSclerosis patientsMouse myelin oligodendrocyte glycoproteinB cell-deficient miceMyelin oligodendrocyte glycoprotein antibodyB cell requirementCell-deficient miceAutoimmune encephalomyelitisAntibody pathogenicityPathogenic IgGC57BL/6 miceGlycoprotein antibodiesControl subjectsOligodendrocyte glycoproteinOnly immunizationMOG proteinHigh titersComparable titersMyelin componentsOligodendrocyte physiologyAntigenic determinantsChronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions
Heikenwalder M, Zeller N, Seeger H, Prinz M, Klöhn P, Schwarz P, Ruddle NH, Weissmann C, Aguzzi A. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions. Science 2005, 307: 1107-1110. PMID: 15661974, DOI: 10.1126/science.1106460.Peer-Reviewed Original ResearchConceptsInflammatory conditionsNormal cellular prion protein PrPCCellular prion protein PrPCChronic lymphocytic inflammationIatrogenic prion transmissionChronic inflammatory conditionsPrion protein PrPCFDC-M1Lymphocytic inflammationEctopic inductionProinflammatory cytokinesInflamed organsImmune cellsInflammatory diseasesInflammatory fociLymphoid tissuePrion accumulationPrion inoculationOrgan tropismPrion pathogenesisPrion replicationTissue distributionPrion transmissionPrionsMiceLymphotoxin Plays a Crucial Role in the Development and Function of Nasal-Associated Lymphoid Tissue through Regulation of Chemokines and Peripheral Node Addressin
Ying X, Chan K, Shenoy P, Hill M, Ruddle NH. Lymphotoxin Plays a Crucial Role in the Development and Function of Nasal-Associated Lymphoid Tissue through Regulation of Chemokines and Peripheral Node Addressin. American Journal Of Pathology 2005, 166: 135-146. PMID: 15632007, PMCID: PMC1602284, DOI: 10.1016/s0002-9440(10)62239-0.Peer-Reviewed Original ResearchConceptsHigh endothelial venulesLymphoid chemokinesIntranasal immunizationNasal-Associated Lymphoid TissueB cell compartmentalizationB cell zonesCervical lymph nodesSerum IgG titersLower cytokine levelsExpression of lymphotoxinImmediate postnatal periodRole of cytokinesRegulation of chemokinesWild-type miceGlyCAM-1Peripheral node addressinLymphoid tissue developmentNALT developmentSplenic cytokinesVaginal IgACytokine levelsLymph nodesIgG titersVascular addressinsLymphoid tissue
2004
IκB Kinase Complex α Kinase Activity Controls Chemokine and High Endothelial Venule Gene Expression in Lymph Nodes and Nasal-Associated Lymphoid Tissue
Drayton DL, Bonizzi G, Ying X, Liao S, Karin M, Ruddle NH. IκB Kinase Complex α Kinase Activity Controls Chemokine and High Endothelial Venule Gene Expression in Lymph Nodes and Nasal-Associated Lymphoid Tissue. The Journal Of Immunology 2004, 173: 6161-6168. PMID: 15528353, DOI: 10.4049/jimmunol.173.10.6161.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationChemokinesEndothelium, LymphaticEnzyme ActivationGene Expression Regulation, DevelopmentalI-kappa B KinaseLigandsLymph NodesLymphoid TissueLymphotoxin beta ReceptorMiceMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsNasal MucosaProtein Serine-Threonine KinasesProtein SubunitsReceptors, Tumor Necrosis FactorConceptsHigh endothelial venulesSecondary lymphoid organogenesisLymph nodesAlternative NF-kappaB pathwayPeripheral node addressinNF-kappaB pathwayLymphoid tissueLymphoid organogenesisNasal-Associated Lymphoid TissueCell adhesion molecule-1Lymphoid chemokines CCL19Adhesion molecule-1GlyCAM-1Lymphotoxin beta receptorPathway activityNALT developmentChemokines CCL19Endothelial venulesBeta receptorsMolecule-1Mutant miceTarget genesCritical roleGene expressionReduced expressionMAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection
Soderberg KA, Linehan MM, Ruddle NH, Iwasaki A. MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection. The Journal Of Immunology 2004, 173: 1908-1913. PMID: 15265924, DOI: 10.4049/jimmunol.173.3.1908.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralCD4-Positive T-LymphocytesCell Adhesion MoleculesDendritic CellsFemaleHerpes GenitalisHerpesvirus 2, HumanImmunoglobulin GImmunoglobulinsLymph NodesLymphocyte ActivationLymphotoxin-alphaLymphotoxin-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMucoproteinsSacrococcygeal RegionSplenectomyT-Cell Antigen Receptor SpecificityTh1 CellsVaginitisConceptsBeta-deficient miceSacral lymph nodesLymph nodesMesenteric lymph nodesWild-type miceGenital mucosaHerpes simplex virus 2 infectionIntravaginal HSV-2 infectionLT alpha-deficient miceMucosal addressin cell adhesion molecule-1Simplex virus 2 infectionCell adhesion molecule-1Mucosal lymph nodesAlpha-deficient miceCervical lymph nodesHSV-2 infectionVirus 2 infectionHSV type 2Potent immune responsesAdhesion molecule-1Intravaginal infectionTh1 responseDendritic cellsIgG responsesIliac artery
2003
Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice
Oliver AR, Lyon GM, Ruddle NH. Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice. The Journal Of Immunology 2003, 171: 462-468. PMID: 12817031, DOI: 10.4049/jimmunol.171.1.462.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAutoantibodiesB-LymphocytesCell MovementDose-Response Relationship, ImmunologicEncephalomyelitis, Autoimmune, ExperimentalFemaleGlycoproteinsHumansImmunoglobulin GInjections, IntramuscularInterferon-gammaInterleukin-13MiceMice, Inbred C57BLMice, Mutant StrainsMolecular Sequence DataMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsRatsSpecies SpecificitySpinal CordConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinRat myelin oligodendrocyte glycoproteinHuman myelin oligodendrocyte glycoproteinMOG 35C57BL/6 miceMOG proteinAutoimmune encephalomyelitisOligodendrocyte glycoproteinB cellsCell responsesEncephalitogenic T cell responsesB cell-deficient miceB cell dependenceCell-deficient miceT cell responsesB cell responsesDifferent pathogenic mechanismsCNS infiltratesIL-13T cellsSpleen cellsIFN-gammaIgG subclassesAg presentation