2023
Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer
Ruddle N. Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer. Current Opinion In Physiology 2023, 36: 100705. PMID: 38523879, PMCID: PMC10956444, DOI: 10.1016/j.cophys.2023.100705.Peer-Reviewed Original ResearchHigh endothelial venulesTertiary lymphoid structuresLymphoid organsEndothelial venulesImmune checkpoint blockadeFavorable clinical outcomeAdhesion molecule-1Peripheral node addressinAutoimmune lesionsCheckpoint blockadeClinical outcomesEffector cellsChronic inflammationLymphoid structuresAcute inflammationLymphoid cellsMolecule-1InflammationCentral memoryAdhesion moleculesBlood vesselsPrecursor cellsImmunotherapyVenulesOrgans
2020
Basics of Inducible Lymphoid Organs
Ruddle NH. Basics of Inducible Lymphoid Organs. Current Topics In Microbiology And Immunology 2020, 426: 1-19. PMID: 32588229, DOI: 10.1007/82_2020_218.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsSecondary lymphoid organsLymphoid tissue organizerHigh endothelial venulesLymphoid organsDendritic cellsB cellsEctopic lymphoid organsFollicular dendritic cellsTertiary lymphoid structuresTertiary lymphoid tissueLymph nodesNK cellsChronic inflammationLTi cellsLymphoid structuresTolerance inductionInducer cellsLymphoid tissueEndothelial venulesAntigen presentationT cellsAccumulation of cellsStromal cellsAutoimmunity
2016
High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation
Ruddle NH. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation. Frontiers In Immunology 2016, 7: 491. PMID: 27881983, PMCID: PMC5101196, DOI: 10.3389/fimmu.2016.00491.Peer-Reviewed Original ResearchTertiary lymphoid organsHigh endothelial venulesSecondary lymphoid organsLymph nodesAntigen-presenting cellsLymphoid organsEndothelial venulesLymphatic vesselsStromal cellsCentral memory cellsPrimary lymphoid organsTransport antigensGraft rejectionEffector cellsChemokine expressionChronic inflammationPeyer's patchesAntigen presentationInflammatory signalsB cellsBone marrowImmune systemReticular cellsMicrobial infectionsCellular compositionTertiary Lymphoid Tissues
Ruddle N. Tertiary Lymphoid Tissues. 2016, 480-485. DOI: 10.1016/b978-0-12-374279-7.07012-0.Peer-Reviewed Original ResearchTertiary lymphoid organsTertiary lymphoid tissueSecondary lymphoid organsLymphoid organsLymphoid tissueConventional lymphoid organsChronic graft rejectionHigh endothelial venulesChronic microbial infectionsStromal cellular compositionAntigen primingNonlymphoid organsGraft rejectionDeterminant spreadingLymph nodesChronic inflammationEndothelial venulesClinical diseaseImmune responseInfectious organismsMicrobial infectionsCellular compositionLymphatic vesselsEctopic sitesAutoimmunity
2013
The development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164)
Kuerten S, Schickel A, Kerkloh C, Recks M, Addicks K, Ruddle N, Lehmann P. The development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164). The Journal Of Immunology 2013, 190: 172.9-172.9. DOI: 10.4049/jimmunol.190.supp.172.9.Peer-Reviewed Original ResearchTertiary lymphoid organsT cell responsesCentral nervous systemExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisCell responsesLymphoid organsNervous systemFormation of TLOsAntigen-specific T cell responsesSecondary progressive multiple sclerosisHuman autoimmune disease multiple sclerosisAutoimmune disease multiple sclerosisT cell compartmentalizationB cell aggregatesChronic disease stageDisease multiple sclerosisSevere clinical diseaseHigh endothelial venulesGerminal center formationMyelin basic proteinAutoimmune encephalomyelitisCNS autoimmunityCortical pathology
2012
Fluorescent transgenic reporter mice can be used for in vivo Imaging of lymphatic vessels and high endothelial venules in a Sjögren’s model (61.7)
Ruddle N, Truman L, Bentley K, Alonso-Gonzalez N. Fluorescent transgenic reporter mice can be used for in vivo Imaging of lymphatic vessels and high endothelial venules in a Sjögren’s model (61.7). The Journal Of Immunology 2012, 188: 61.7-61.7. DOI: 10.4049/jimmunol.188.supp.61.7.Peer-Reviewed Original ResearchTertiary lymphoid organsLymphocyte infiltrationSjögren's syndromeLymphatic vesselsReporter miceTransgenic miceB cell compartmentalizationSalivary glandsExtra-nodal lymphomaHigh endothelial venulesMinor salivary glandsEGFP reporter miceTransgenic reporter miceAntigen primingSjögren's patientsVascular changesAutoantibody productionBL/6 miceAutoimmune diseasesLymphoid organsSpontaneous lymphomasEndothelial venulesGerminal centersLymph flowImmature phenotypeProxTom 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 utilityFollicular dendritic cells, conduits, lymphatic vessels, and high endothelial venules in tertiary lymphoid organs: Parallels with lymph node stroma
Stranford S, Ruddle NH. Follicular dendritic cells, conduits, lymphatic vessels, and high endothelial venules in tertiary lymphoid organs: Parallels with lymph node stroma. Frontiers In Immunology 2012, 3: 350. PMID: 23230435, PMCID: PMC3515885, DOI: 10.3389/fimmu.2012.00350.Peer-Reviewed Original ResearchSecondary lymphoid organsFollicular dendritic cellsHigh endothelial venulesLymph nodesDendritic cellsChronic inflammationLymphoid organsLymphoid tissueEndothelial venulesTertiary lymphoid organsAnti-tumor responseEctopic lymphoid tissueLymph node stromaTertiary lymphoid tissueNon-lymphoid organsLymphatic vesselsAutoimmune activityGraft rejectionAutoimmune responseInflammatory signalsTransgenic miceTherapeutic interventionsReticular cellsStromal componentsVivo real time
2008
Antigen‐induced Lymph Node Remodeling: LVs, HEVs and Conduits
Stranford S, Liao S, Bentley K, Ruddle F, Ruddle N. Antigen‐induced Lymph Node Remodeling: LVs, HEVs and Conduits. The FASEB Journal 2008, 22: 392.3-392.3. DOI: 10.1096/fasebj.22.1_supplement.392.3.Peer-Reviewed Original ResearchHigh endothelial venulesLymph nodesAntigen encounterLymphatic vesselsLymph node remodelingLYVE-1T cell areasSecondary lymphoid organsAntigen-specific lymphocytesER-TR7Lymphoid organsAfferent lymphaticsEndothelial venulesMice transgenicTransgenic miceVascular interactionsDay 4Endothelial cellsAbluminal surfaceLymphocytesAntigenMarkersExpressionEGFP expressionVessels
2007
Transgenic 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 techniques
2006
Synchrony 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
Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection
Baddoura FK, Nasr IW, Wrobel B, Li Q, Ruddle NH, Lakkis FG. Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection. American Journal Of Transplantation 2005, 5: 510-516. PMID: 15707405, DOI: 10.1111/j.1600-6143.2004.00714.x.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsHigh endothelial venulesMurine cardiac allograftsLymphoid neogenesisPeripheral node addressinChronic rejectionCardiac allograftsLymphoid accumulationsLocal T cell activationB cell zonesChronic allograft rejectionT cell activationAcute rejectionAllograft rejectionLymph nodesChronic autoimmunityImmune pathologyLocal antigensLymphoid organsEndothelial venulesNonlymphoid tissuesTransplanted organsAllograftsTarget organsNeogenesisLymphotoxin 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 expressionDetection of a Sulfotransferase (HEC-GlcNAc6ST) in High Endothelial Venules of Lymph Nodes and in High Endothelial Venule-Like Vessels within Ectopic Lymphoid Aggregates Relationship to the MECA-79 Epitope
Bistrup A, Tsay D, Shenoy P, Singer MS, Bangia N, Luther SA, Cyster JG, Ruddle NH, Rosen SD. Detection of a Sulfotransferase (HEC-GlcNAc6ST) in High Endothelial Venules of Lymph Nodes and in High Endothelial Venule-Like Vessels within Ectopic Lymphoid Aggregates Relationship to the MECA-79 Epitope. American Journal Of Pathology 2004, 164: 1635-1644. PMID: 15111310, PMCID: PMC1615668, DOI: 10.1016/s0002-9440(10)63722-4.Peer-Reviewed Original ResearchConceptsHigh endothelial venulesMECA-79 epitopeLymph nodesMECA-79Endothelial venulesHEC-GlcNAc6STHigh Endothelial Venule-Like VesselsLuminal stainingL-selectinMECA-79 monoclonal antibodyNull miceNonobese diabetic (NOD) miceHEV-like vesselsLymph nodes resultsHigh endothelial cellsLymphoid neogenesisDiabetic miceLymphocyte rollingLymphocyte homingMonoclonal antibodiesEndothelial cellsMiceConcomitant expressionEpitopesVenules
2003
Ectopic LTαβ Directs Lymphoid Organ Neogenesis with Concomitant Expression of Peripheral Node Addressin and a HEV-restricted Sulfotransferase
Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH. Ectopic LTαβ Directs Lymphoid Organ Neogenesis with Concomitant Expression of Peripheral Node Addressin and a HEV-restricted Sulfotransferase. Journal Of Experimental Medicine 2003, 197: 1153-1163. PMID: 12732657, PMCID: PMC2193975, DOI: 10.1084/jem.20021761.Peer-Reviewed Original ResearchConceptsHigh endothelial venulesPeripheral node addressinLymphoid organogenesisLT-alphaB cell compartmentalizationMucosal addressin cell adhesion moleculeAlpha betaLymph node functionB-cell areasAntigen presenting cellsLymphoid neogenesisPancreatic infiltratesPNAd expressionLymphoid chemokinesFDC networksMononuclear infiltrateAlpha micePresenting cellsEndothelial venulesCell adhesion moleculeCell accumulationLT-betaAdhesion moleculesNode functionPancreata
2001
Sulfation of L-Selectin Ligands by an HEV-Restricted Sulfotransferase Regulates Lymphocyte Homing to Lymph Nodes
Hemmerich S, Bistrup A, Singer M, van Zante A, Lee J, Tsay D, Peters M, Carminati J, Brennan T, Carver-Moore K, Leviten M, Fuentes M, Ruddle N, Rosen S. Sulfation of L-Selectin Ligands by an HEV-Restricted Sulfotransferase Regulates Lymphocyte Homing to Lymph Nodes. Immunity 2001, 15: 237-247. PMID: 11520459, DOI: 10.1016/s1074-7613(01)00188-1.Peer-Reviewed Original ResearchConceptsHigh endothelial venulesLymph nodesL-selectinLuminal aspectChronic inflammatory sitesHEC-GlcNAc6STImportant therapeutic targetL-selectin ligandsMECA-79Lymphocyte traffickingEndothelial venulesInflammatory sitesTherapeutic targetLymphocyte homingLymphocyte bindingGenetic deletionSpecific ligandsLigand activityRecombinant L-selectinSulfotransferaseCritical roleEssential posttranslational modificationVenules