2023
Posttransplant Tertiary Lymphoid Organs
Ruddle N. Posttransplant Tertiary Lymphoid Organs. Transplantation 2023, 108: 1090-1099. PMID: 37917987, PMCID: PMC11042531, DOI: 10.1097/tp.0000000000004812.Peer-Reviewed Original ResearchTertiary lymphoid organsOrgan rejectionLymphoid organsCase of immunosuppressionEctopic lymphoid structuresDevelopment of lymphomaLymphoid neogenesisLymph nodesIschemic reperfusionChronic inflammationLymphoid structuresNephrotoxic agentsTumor antigensVascular componentLymphoid cellsTherapeutic manipulationSustained exposureMicrobial infectionsCellular compositionStaging schemeCancerOrgansRejectionImmunosuppressionReperfusion
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 compositionLymphotoxin
Ruddle N. Lymphotoxin. 2016, 466-475. DOI: 10.1016/b978-0-12-374279-7.10003-7.Peer-Reviewed Original ResearchTumor necrosis factorNFκB pathwayChronic inflammatory infiltrateAlternative NFκB pathwayMajor histocompatibility complexLymph nodesInflammatory infiltrateChemokine expressionChronic inflammationLymphoid organsNecrosis factorImmune responseCanonical NFκB pathwaySpecific antigenTNF receptorLymphotoxinLTβ receptorHistocompatibility complexTNF familyCulture supernatantsEmbryological developmentLymphocytesLTαCytotoxic activityReceptorsTertiary 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
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
2012
ProxTom 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
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 mechanisms
2010
Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs
Penaranda C, Tang Q, Ruddle NH, Bluestone JA. Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs. Diabetes 2010, 59: 1461-1468. PMID: 20299465, PMCID: PMC2874707, DOI: 10.2337/db09-1129.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsPancreatic lymph nodesNOD miceLymph nodesDiabetes developmentDiabetic miceLymphoid organsSpontaneous type 1 diabetesB cell compartmentalizationExit of lymphocytesNonobese diabetic (NOD) miceAge-matched miceDevelopment of diabetesPrevention of diabetesNaive T cellsType 1 diabetesB cell compartmentWeeks of ageSignificant insulitisIslet destructionTreatment withdrawalAutoimmune destructionClinical scoresAccelerated diseaseDisease progression
2009
Secondary Lymphoid Organs: Responding to Genetic and Environmental Cues in Ontogeny and the Immune Response
Ruddle NH, Akirav EM. Secondary Lymphoid Organs: Responding to Genetic and Environmental Cues in Ontogeny and the Immune Response. The Journal Of Immunology 2009, 183: 2205-2212. PMID: 19661265, PMCID: PMC2766168, DOI: 10.4049/jimmunol.0804324.Peer-Reviewed Original ResearchConceptsSecondary lymphoid organsLymphoid tissueLymphoid organsImmune responseLymphoid tissue organizer cellsBronchus-associated lymphoid tissueLymphoid tissue inducerTertiary lymphoid tissueSLO developmentLymphoid chemokinesIL-17Lymph nodesLymphoid folliclesPeyer's patchesIL-7Crucial cytokineMucosal tissuesOrganizer cellsCellular accumulationCytokinesTissueOrgansEnvironmental cuesCryptopatchesAdenoids
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
2006
Lymphoid organ development: from ontogeny to neogenesis
Drayton DL, Liao S, Mounzer RH, Ruddle NH. Lymphoid organ development: from ontogeny to neogenesis. Nature Immunology 2006, 7: 344-353. PMID: 16550197, DOI: 10.1038/ni1330.Peer-Reviewed Original ResearchConceptsBronchial-associated lymphoid tissueTertiary lymphoid organsSecondary lymphoid organsLymphoid organsLymphoid tissueNasal-associated lymphoid tissueSpecific developmentalCellular accumulationLymphoid neogenesisLymph nodesChronic inflammationPeyer's patchesAnatomic locationOntogenyEnvironmental influencesOrgansTissue
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 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 arteryDetection 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
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 modificationVenulesInduction of oral tolerance to cellular immune responses in the absence of Peyer's patches
Spahn T, Fontana A, Faria A, Slavin A, Eugster H, Zhang X, Koni P, Ruddle N, Flavell R, Rennert P, Weiner H. Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. European Journal Of Immunology 2001, 31: 1278-1287. PMID: 11298355, DOI: 10.1002/1521-4141(200104)31:4<1278::aid-immu1278>3.0.co;2-a.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAntibodiesDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayFecesGene DeletionHypersensitivity, DelayedImmune ToleranceImmunity, MucosalImmunoglobulin AInterferon-gammaInterleukin-2Lymph NodesLymphotoxin-alphaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutOvalbuminPeyer's PatchesSignal TransductionTumor Necrosis Factor-alphaConceptsGut-associated lymphoid tissueMesenteric lymph nodesOral toleranceLow-dose oral toleranceDelayed-type hypersensitivity responseFecal IgA productionLTbeta-/- miceOral tolerance inductionLamina propria lymphocytesIntact immune systemCellular immune responsesPeripheral lymphoid organsIFN-gamma productionTumor necrosis factor familyProcessing of antigensNecrosis factor familySystemic hyporesponsivenessLymph nodesHypersensitivity responseTolerance inductionIgA productionIntraperitoneal administrationLymphoid organsLymphoid tissuePeyer's patches