2020
Lymphotoxin targeted to salivary and lacrimal glands induces tertiary lymphoid organs and cervical lymphadenopathy and reduces tear production
Truman LA, Bentley KL, Ruddle NH. Lymphotoxin targeted to salivary and lacrimal glands induces tertiary lymphoid organs and cervical lymphadenopathy and reduces tear production. European Journal Of Immunology 2020, 50: 418-425. PMID: 32012252, DOI: 10.1002/eji.201948300.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsLacrimal glandCervical lymphadenopathySjögren's syndromeLymphoid organsTear productionRole of lymphotoxinTLO formationAutoantibody titresMALT lymphomaLymphoid tissueTransgenic miceLymphotoxinMiceLymphadenopathyGlandSyndromeOrgansAutoimmunityMucosalLymphomaLTαTitresSalivaryLTβ
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
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
A yeast‐based recombinogenic targeting toolset for transgenic analysis of human disease genes
Bentley KL, Shashikant CS, Wang W, Ruddle NH, Ruddle FH. A yeast‐based recombinogenic targeting toolset for transgenic analysis of human disease genes. Annals Of The New York Academy Of Sciences 2010, 1207: e58-e68. PMID: 20961307, DOI: 10.1111/j.1749-6632.2010.05712.x.Peer-Reviewed Original ResearchConceptsPolycystic kidney disease 1Yeast-bacterial shuttle vectorHuman disease genesFunction of genesLarge insert DNABacterial artificial chromosomeGene of interestTransgenic analysisGenomic fragmentArtificial chromosomesDNA insertsDisease genesBiological processesShuttle vectorHuman diseasesGenesGene modificationClaspettesPClasperMouse modelValuable resourceTransgenic mouse modelTransgenic miceCritical insightsImmune system
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 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 Gland
2005
Chronic 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 transmissionPrionsMice
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
2000
Lymphoid Tissue Homing Chemokines Are Expressed in Chronic Inflammation
Hjelmström P, Fjell J, Nakagawa T, Sacca R, Cuff C, Ruddle N. Lymphoid Tissue Homing Chemokines Are Expressed in Chronic Inflammation. American Journal Of Pathology 2000, 156: 1133-1138. PMID: 10751336, PMCID: PMC1876894, DOI: 10.1016/s0002-9440(10)64981-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDChemokine CCL21Chemokine CXCL13Chemokines, CCChemokines, CXCChronic DiseaseFemaleInflammationLymphotoxin-alphaLymphotoxin-betaMembrane ProteinsMiceMice, Inbred NODMice, TransgenicPancreasPancreatitisProtein IsoformsReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type IRNA, MessengerConceptsSecondary lymphoid tissue chemokineB lymphocyte chemoattractantExpression of SLCChronic inflammationLymphoid organsPrediabetic nonobese diabetic (NOD) micePrediabetic NOD miceLymphoid tissue chemokineNonobese diabetic (NOD) miceChronic inflammatory diseaseSecondary lymphoid organsTrafficking of lymphocytesTumor necrosis factor receptor 1Necrosis factor receptor 1Factor receptor 1Homing ChemokinesLymphocyte chemoattractantLymphoid neogenesisNOD miceDendritic cellsDiabetic miceInflammatory diseasesInflammatory processLymphoid tissueInflamed tissues
1996
The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice
Flavell RA, Kratz A, Ruddle NH. The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice. Current Topics In Microbiology And Immunology 1996, 206: 33-50. PMID: 8608724, DOI: 10.1007/978-3-642-85208-4_3.Peer-Reviewed Original ResearchConceptsInsulin-dependent diabetes mellitusTumor necrosis factor-transgenic (TNF-Tg) miceDevelopment of diabetesHLA susceptibility allelesIslets of LangerhansHLA-DQβDiabetes mellitusFrank diabetesTransgenic miceStrong associationSusceptibility allelesDiabetesIdentical twinsDiseaseInsulinIsletsInsulitisSite of synthesisMellitusNumber of yearsPatientsMiceEnvironmental factors
1993
Mice Transgenic for HTLV-I LTR-tax Exhibit Tax Expression in Bone, Skeletal Alterations, and High Bone Turnover
Ruddle N, Li C, Horn W, Santiago P, Troiano N, Jay G, Horowitz M, Baron R. Mice Transgenic for HTLV-I LTR-tax Exhibit Tax Expression in Bone, Skeletal Alterations, and High Bone Turnover. Virology 1993, 197: 196-204. PMID: 8212554, DOI: 10.1006/viro.1993.1580.Peer-Reviewed Original ResearchConceptsHigh bone turnoverHTLV-I infectionBone turnoverMice transgenicSkeletal alterationsAdult T-cell leukemiaMonths of ageSpindle-shaped cellsT-cell leukemiaBone cell activityPaget's diseaseViral etiologyOsteoclast numberBone resorptionPathogenetic mechanismsBone diseaseCell leukemiaBone marrowCell activitySkeletal changesTax mRNASevere skeletal abnormalitiesHost factorsDiseaseSkeletal abnormalitiesTransgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. The Journal Of Immunology 1993, 150: 4136-50. PMID: 7682590, DOI: 10.4049/jimmunol.150.9.4136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceCD4 AntigensCD8 AntigensCell Adhesion MoleculesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IIHumansIntercellular Adhesion Molecule-1Islets of LangerhansKidneyLeukocyte Common AntigensLymphotoxin-alphaMiceMice, Inbred NODMice, TransgenicPancreatitisProtein Tyrosine Phosphatase, Non-Receptor Type 1Receptors, Interleukin-2Tumor Necrosis Factor-alphaUp-RegulationConceptsTNF-alphaTransgenic miceTNF-alpha transgenic miceInsulin-dependent diabetes mellitusAdhesion molecules VCAM-1Rat insulin II promoterTNF-alpha transgeneRole of TNFMurine TNF-alphaTumor necrosis factorRegulation of inflammationMHC class IReduced insulin contentPeri-insulitisIslet destructionDiabetes mellitusAutoimmune diseasesAlpha productionIslet endotheliumNecrosis factorT cellsICAM-1VCAM-1Insulin contentB cellsProbing the mechanism of TNF-α(cachectin)- and TNF-β(lymphotoxin)-induced pancreatic inflammation with transgenic mice
Ruddle NH, Picarella D, Kratz A, Li C, Flavell RA. Probing the mechanism of TNF-α(cachectin)- and TNF-β(lymphotoxin)-induced pancreatic inflammation with transgenic mice. Research In Immunology 1993, 144: 336-342. PMID: 8278655, DOI: 10.1016/s0923-2494(93)80077-c.Peer-Reviewed Original Research
1992
Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 10036-10040. PMID: 1279667, PMCID: PMC50272, DOI: 10.1073/pnas.89.21.10036.Peer-Reviewed Original ResearchConceptsNecrosis factor betaTransgenic miceFactor betaInsulin-dependent diabetes mellitusRat insulin II promoterTumor necrosis factor betaType 1 diabetesRegulation of inflammationTNF-beta geneDiabetes mellitusInflammatory infiltrateInflammatory diseasesT cellsImmune responseB cellsInsulitisDiabetesMicePancreasImportant early stepBetaEarly stagesCD8InfiltratesMellitus