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
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
2014
Lymphatic vessels and tertiary lymphoid organs
Ruddle NH. Lymphatic vessels and tertiary lymphoid organs. Journal Of Clinical Investigation 2014, 124: 953-959. PMID: 24590281, PMCID: PMC3934190, DOI: 10.1172/jci71611.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesHumansInflammationLymph NodesLymphatic VesselsLymphedemaNeoplasms
2013
Identification of a New Stromal Cell Type Involved in the Regulation of Inflamed B Cell Follicles
Mionnet C, Mondor I, Jorquera A, Loosveld M, Maurizio J, Arcangeli ML, Ruddle NH, Nowak J, Aurrand-Lions M, Luche H, Bajénoff M. Identification of a New Stromal Cell Type Involved in the Regulation of Inflamed B Cell Follicles. PLOS Biology 2013, 11: e1001672. PMID: 24130458, PMCID: PMC3794863, DOI: 10.1371/journal.pbio.1001672.Peer-Reviewed Original ResearchConceptsStromal cell typesB cell folliclesT cell zonesCell typesFate-mapping systemStromal cellsCellular demandB cellsLymph Node Stromal CellsSurvival signalsStromal cell subsetsB cell ablationLN stromal cellsCell zoneAdhesive substrataCell ablationCell subsetsImmune responseCellsFolliclesInflammationSubstrataRegulationTransient boundaryLymphocytesLymphatic 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
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 utility
2010
High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature
Bentley KL, Stranford S, Liao S, Mounzer RM, Ruddle FH, Ruddle NH. High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature. Advances In Experimental Medicine And Biology 2010, 691: 35-44. PMID: 21153307, DOI: 10.1007/978-1-4419-6612-4_4.Peer-Reviewed Original Research
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 techniques
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 ResearchMeSH KeywordsAnimalsAutoimmunityFemaleHumansLymph NodesLymphangiogenesisPregnancyTumor Necrosis Factor-alphaConceptsBronchial-associated lymphoid tissueTertiary lymphoid organsSecondary lymphoid organsLymphoid organsLymphoid tissueNasal-associated lymphoid tissueSpecific developmentalCellular accumulationLymphoid neogenesisLymph nodesChronic inflammationPeyer's patchesAnatomic locationOntogenyEnvironmental influencesOrgansTissue
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
2002
Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ
Constant SL, Brogdon JL, Piggott DA, Herrick CA, Visintin I, Ruddle NH, Bottomly K. Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. Journal Of Clinical Investigation 2002, 110: 1441-1448. PMID: 12438442, PMCID: PMC151814, DOI: 10.1172/jci16109.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsAntigen PresentationAntigen-Presenting CellsAntigens, ProtozoanCD4-Positive T-LymphocytesCell DifferentiationCell MovementCytokinesInterleukin-10Interleukin-6Leishmania majorLungLymph NodesLymphotoxin-alphaMiceMice, Inbred C57BLMice, KnockoutTh1 CellsTh2 CellsConceptsAntigen-presenting cellsTh2 T cell differentiationT cell primingT cell differentiationCell primingAntigen-loaded antigen-presenting cellsLung antigen-presenting cellsPulmonary antigen-presenting cellsResident antigen-presenting cellsPreferential primingAntigen-specific T cellsSecondary lymphoid organsTh2-dominated responsesTh1 responseAntigen exposureIL-10Th2 typeAntigen uptakeIL-6Lung microenvironmentLymphoid organsTh2 cellsIntranasal deliveryLung tissueAirway epithelium
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 patchesICOS co-stimulatory receptor is essential for T-cell activation and function
Dong C, Juedes A, Temann U, Shresta S, Allison J, Ruddle N, Flavell R. ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 2001, 409: 97-101. PMID: 11343121, DOI: 10.1038/35051100.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibody FormationAntigens, CDAntigens, Differentiation, T-LymphocyteCell DifferentiationCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalGene TargetingHemocyaninsInducible T-Cell Co-Stimulator ProteinInterleukin-13Interleukin-4Lymph NodesLymphocyte ActivationMiceMice, KnockoutMolecular Sequence DataMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinT-LymphocytesConceptsInducible co-stimulatory moleculeT cell activationCo-stimulatory moleculesT cellsICOS-/- miceICOS-deficient miceInflammatory autoimmune diseaseExperimental autoimmune encephalomyelitisInjection of lipopolysaccharideCo-stimulatory receptorsHumoral immune responseNon-immune tissuesT lymphocyte activationAutoimmune encephalomyelitisAutoimmune diseasesImmune responseInterleukin-4Immune functionCD28/CTLA4 familyB cellsProtective roleEnhanced susceptibilityActivationReceptorsHigh affinity
1999
Lymphoid neoorganogenesis
Ruddle N. Lymphoid neoorganogenesis. Immunologic Research 1999, 19: 119-125. PMID: 10493167, DOI: 10.1007/bf02786481.Peer-Reviewed Original ResearchConceptsVascular cell adhesion moleculeE-selectin adhesion moleculesIntercellular adhesion moleculePeripheral node addressinAdhesion moleculesKnockout miceTertiary lymphoid organsCellular adhesion moleculesNecrosis factor familyLymphoid organ developmentEndothelial cell lineAutoimmune diseasesChronic inflammationLymphoid organsLymphoid tissueCell adhesion moleculeLymphotoxinInflammationMultiple receptorsMicrobial infectionsCell linesMiceOrgan developmentFactor familyAddressin
1994
Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin
De Togni P, Goellner J, Ruddle N, Streeter P, Fick A, Mariathasan S, Smith S, Carlson R, Shornick L, Strauss-Schoenberger J, Russell J, Karr R, Chaplin D. Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin. Science 1994, 264: 703-707. PMID: 8171322, DOI: 10.1126/science.8171322.Peer-Reviewed Original ResearchConceptsPeripheral lymphoid organsPeripheral bloodLymphoid organsT cellsDetectable lymph nodesT cell subsetsLymph nodesCD4-CD8Cell subsetsPeyer's patchesMice DeficientImmunoglobulin MWhite pulpLymphotoxinLytic functionNormal ratioAbnormal developmentSpleenStem cellsBloodNormal developmentOrgansCellsLymphocytesThymus
1971
Experimental autoallergic encephalomyelitis and cellular hypersensitivity in vitro.
Ellison G, Waksman B, Ruddle N. Experimental autoallergic encephalomyelitis and cellular hypersensitivity in vitro. Neurology 1971, 21: 778-82. PMID: 5106293, DOI: 10.1212/wnl.21.8.778.Peer-Reviewed Original Research