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
2016
The lymphotoxin β receptor is a potential therapeutic target in renal inflammation
Seleznik G, Seeger H, Bauer J, Fu K, Czerkowicz J, Papandile A, Poreci U, Rabah D, Ranger A, Cohen CD, Lindenmeyer M, Chen J, Edenhofer I, Anders HJ, Lech M, Wüthrich RP, Ruddle NH, Moeller MJ, Kozakowski N, Regele H, Browning JL, Heikenwalder M, Segerer S. The lymphotoxin β receptor is a potential therapeutic target in renal inflammation. Kidney International 2016, 89: 113-126. PMID: 26398497, DOI: 10.1038/ki.2015.280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCell LineChemokinesDisease Models, AnimalEpithelial CellsFemaleGlomerulonephritis, IGAHumansImmunoglobulinsKidney GlomerulusKidney TubulesLigandsLupus NephritisLymphocytesLymphotoxin beta ReceptorLymphotoxin-alphaLymphotoxin-betaMaleMesangial CellsMiceMiddle AgedRNA, MessengerSignal TransductionTranscriptomeConceptsTubular epithelial cellsParietal epithelial cellsEpithelial cellsRenal injuryLTβR signalingTherapeutic targetGlomerular immune complex depositionLymphotoxin β receptor (LTβR) signalingImproved renal functionSerum autoantibody titersHuman tubular epithelial cellsImmune complex depositionMurine lupus modelsProgressive kidney diseaseSuitable therapeutic targetPreclinical mouse modelsDifferent renal compartmentsPotential therapeutic targetΒ Receptor SignalingLymphotoxin β receptorAutoantibody titersRenal inflammationLupus modelsRenal functionRenal biopsy
2014
Pillars article: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994. 264: 703-707.
De Togni P, Goellner J, Ruddle NH, Streeter PR, Andrea F, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J, Russell JH, Karr R, Chaplin DD. Pillars article: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994. 264: 703-707. The Journal Of Immunology 2014, 192: 2010-4. PMID: 24563504.Peer-Reviewed Original ResearchLymphotoxin and TNF: How it all began—A tribute to the travelers
Ruddle NH. Lymphotoxin and TNF: How it all began—A tribute to the travelers. Cytokine & Growth Factor Reviews 2014, 25: 83-89. PMID: 24636534, PMCID: PMC4027955, DOI: 10.1016/j.cytogfr.2014.02.001.Peer-Reviewed Original Research
2010
Lymphotoxin-alpha contributes to lymphangiogenesis
Mounzer RH, Svendsen OS, Baluk P, Bergman CM, Padera TP, Wiig H, Jain RK, McDonald DM, Ruddle NH. Lymphotoxin-alpha contributes to lymphangiogenesis. Blood 2010, 116: 2173-2182. PMID: 20566898, PMCID: PMC2951858, DOI: 10.1182/blood-2009-12-256065.Peer-Reviewed Original Research
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 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
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
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
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
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 epitheliumRole of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection
Suresh M, Lanier G, Large MK, Whitmire JK, Altman JD, Ruddle NH, Ahmed R. Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection. Journal Of Virology 2002, 76: 3943-3951. PMID: 11907234, PMCID: PMC136110, DOI: 10.1128/jvi.76.8.3943-3951.2002.Peer-Reviewed Original ResearchConceptsT cell responsesCD8 T cellsLymphocytic choriomeningitis virusT cellsT cell activationLymphoid architectureMajor histocompatibility complex class I tetramersVirus-specific CD8 T cell responsesLCMV-specific CD8 T cellsLCMV-specific T-cell responsesVirus-specific CD8 T cellsAntigen-specific T cell responsesCD8 T cell responsesLCMV-specific T cellsT cell-mediated immunopathologyLTalpha-deficient miceClass I tetramersAcute viral infectionCD4 T cellsAdoptive transfer experimentsCell transfer experimentsLCMV clearanceNonlymphoid organsAdoptive transferAcute infectionLymphocyte Trafic in Lymphoid Organ Neogenesis
Drayton DL, Chan K, Lesslauer W, Lee J, Ying M, Ruddle NH. Lymphocyte Trafic in Lymphoid Organ Neogenesis. Advances In Experimental Medicine And Biology 2002, 512: 43-48. PMID: 12405186, DOI: 10.1007/978-1-4615-0757-4_6.Peer-Reviewed Original Research
2001
Induction 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 patchesLymphotoxin-alpha deficiency completely protects C57BL/6 mice from developing clinical experimental autoimmune myasthenia gravis
Goluszko E, Hjelmström P, Deng C, Poussin M, Ruddle N, Christadoss P. Lymphotoxin-alpha deficiency completely protects C57BL/6 mice from developing clinical experimental autoimmune myasthenia gravis. Journal Of Neuroimmunology 2001, 113: 109-118. PMID: 11137582, DOI: 10.1016/s0165-5728(00)00420-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAutoantibodiesB7-2 AntigenGene ExpressionImmunodominant EpitopesImmunoglobulin GImmunoglobulin MLymphotoxin-alphaMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMyasthenia Gravis, Autoimmune, ExperimentalReceptors, CholinergicReceptors, Tumor Necrosis FactorSpleenConceptsExperimental autoimmune myasthenia gravisClinical experimental autoimmune myasthenia gravisAutoimmune myasthenia gravisMyasthenia gravisMean titersPrimary humoral immune responseAlpha-deficient miceAnti-AChR antibodiesHumoral immune responseLower mean titersC57BL/6 miceImmunized miceTotal IgGDeficient miceIgG isotypeImmune responseAcetylcholine receptorsPartial preventionGravisMiceComplete preventionTitersLtPreventionPathogenesis
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
1999
Lymphoid neoorganogenesis
Ruddle N. Lymphoid neoorganogenesis. Immunologic Research 1999, 19: 119-125. PMID: 10493167, DOI: 10.1007/bf02786481.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityEmbryonic and Fetal DevelopmentHumansInflammationLymph NodesLymphotoxin-alphaMiceRatsTumor Necrosis Factor-alphaConceptsVascular 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
1997
A Critical Role for Lymphotoxin in Experimental Allergic Encephalomyelitis
Suen W, Bergman C, Hjelmström P, Ruddle N. A Critical Role for Lymphotoxin in Experimental Allergic Encephalomyelitis. Journal Of Experimental Medicine 1997, 186: 1233-1240. PMID: 9334362, PMCID: PMC2199100, DOI: 10.1084/jem.186.8.1233.Peer-Reviewed Original ResearchConceptsExperimental allergic encephalomyelitisMaximum clinical scoreMyelin oligodendrocyte glycoproteinClinical scoresLT-alphaAllergic encephalomyelitisMultiple sclerosisCentral nervous system inflammationNervous system inflammationT cell productionDisease multiple sclerosisRat myelin oligodendrocyte glycoproteinAverage clinical scoreDisease indexWild-type littermatesWT T cellsNecrosis factor familyMOG 35CNS inflammationMOG antibodiesSystem inflammationWT miceC57BL/6 miceOligodendrocyte glycoproteinTNF-alpha