2024
Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities
Ruddle N. Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities. Methods In Molecular Biology 2024, 2864: 299-312. PMID: 39527229, DOI: 10.1007/978-1-0716-4184-2_16.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsTertiary lymphoid structuresSecondary lymphoid organsTA-TLSSusceptibility to immune-related adverse eventsAssociated with favorable clinical outcomesPositive response to immunotherapyResponse to immunotherapyFavorable clinical outcomesCellular compositionVascular growth factorsAccumulation of lymphoid cellsCheckpoint inhibitorsLymphoid neogenesisLymphoid structuresProcess of lymphoid neogenesisClinical outcomesAdenovirus vectorLymphoid cellsTumor-associatedAdverse eventsTumor environmentOrgan rejectionChronic inflammation
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
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
A Humanized Mouse Model of Autoimmune Insulitis
Milam A, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL. A Humanized Mouse Model of Autoimmune Insulitis. Diabetes 2014, 63: 1712-1724. PMID: 24478396, PMCID: PMC3994947, DOI: 10.2337/db13-1141.Peer-Reviewed Original ResearchConceptsT cellsDiabetic donorsInsulin stainingMouse modelAntigen-pulsed cellsAutoantigen-derived peptidesNOD mouse modelHumanized mouse modelType 1 diabetesPancreatic β-cellsT cell linesHuman T cellsIslet infiltrationAutoimmune diabetesNOD-SCIDAutoimmune insulitisHuman diabetesDestructive infiltrationMouse isletsMechanism of inductionΒ-cellsDiabetesDiabetes researchDisease modelsInsulitisLymphatic 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 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
2012
A Switch in Pathogenic Mechanism in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in IFN-γ–Inducible Lysosomal Thiol Reductase-Free Mice
Bergman CM, Marta CB, Maric M, Pfeiffer SE, Cresswell P, Ruddle NH. A Switch in Pathogenic Mechanism in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in IFN-γ–Inducible Lysosomal Thiol Reductase-Free Mice. The Journal Of Immunology 2012, 188: 6001-6009. PMID: 22586035, PMCID: PMC4133136, DOI: 10.4049/jimmunol.1101898.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen-Presenting CellsEncephalomyelitis, Autoimmune, ExperimentalFluorescent Antibody TechniqueGlycoproteinsHumansImmunoblottingMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMyelin ProteinsMyelin-Oligodendrocyte GlycoproteinOxidoreductasesOxidoreductases Acting on Sulfur Group DonorsPeptide FragmentsRatsSequence Homology, Amino Acid
2010
The role of AIRE in human autoimmune disease
Akirav EM, Ruddle NH, Herold KC. The role of AIRE in human autoimmune disease. Nature Reviews Endocrinology 2010, 7: 25-33. PMID: 21102544, DOI: 10.1038/nrendo.2010.200.Peer-Reviewed Original ResearchWorkshop Summary: Roles of the TNF Family in Normal Development and Cancer
Ruddle NH. Workshop Summary: Roles of the TNF Family in Normal Development and Cancer. Advances In Experimental Medicine And Biology 2010, 691: 3-4. PMID: 21153304, DOI: 10.1007/978-1-4419-6612-4_1.Peer-Reviewed Original ResearchA 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 systemPrevention 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
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 Research
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
Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology
Marta CB, Oliver AR, Sweet RA, Pfeiffer SE, Ruddle NH. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13992-13997. PMID: 16172404, PMCID: PMC1236555, DOI: 10.1073/pnas.0504979102.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAutoantibodiesB-LymphocytesEncephalomyelitis, Autoimmune, ExperimentalGlycosylationHumansImmunizationImmunodominant EpitopesImmunoglobulin GMiceMice, Inbred C57BLMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinOligodendrogliaProlineRatsSerineConceptsHuman myelin oligodendrocyte glycoproteinMyelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisAnti-MOG antibodiesMultiple sclerosis patientsSclerosis patientsMouse myelin oligodendrocyte glycoproteinB cell-deficient miceMyelin oligodendrocyte glycoprotein antibodyB cell requirementCell-deficient miceAutoimmune encephalomyelitisAntibody pathogenicityPathogenic IgGC57BL/6 miceGlycoprotein antibodiesControl subjectsOligodendrocyte glycoproteinOnly immunizationMOG proteinHigh titersComparable titersMyelin componentsOligodendrocyte physiologyAntigenic determinants
2003
Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice
Oliver AR, Lyon GM, Ruddle NH. Rat and Human Myelin Oligodendrocyte Glycoproteins Induce Experimental Autoimmune Encephalomyelitis by Different Mechanisms in C57BL/6 Mice. The Journal Of Immunology 2003, 171: 462-468. PMID: 12817031, DOI: 10.4049/jimmunol.171.1.462.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigen PresentationAutoantibodiesB-LymphocytesCell MovementDose-Response Relationship, ImmunologicEncephalomyelitis, Autoimmune, ExperimentalFemaleGlycoproteinsHumansImmunoglobulin GInjections, IntramuscularInterferon-gammaInterleukin-13MiceMice, Inbred C57BLMice, Mutant StrainsMolecular Sequence DataMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsRatsSpecies SpecificitySpinal CordConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinRat myelin oligodendrocyte glycoproteinHuman myelin oligodendrocyte glycoproteinMOG 35C57BL/6 miceMOG proteinAutoimmune encephalomyelitisOligodendrocyte glycoproteinB cellsCell responsesEncephalitogenic T cell responsesB cell-deficient miceB cell dependenceCell-deficient miceT cell responsesB cell responsesDifferent pathogenic mechanismsCNS infiltratesIL-13T cellsSpleen cellsIFN-gammaIgG subclassesAg presentation
2002
Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice
Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice. Journal Of Clinical Investigation 2002, 109: 383-392. PMID: 11827998, PMCID: PMC150854, DOI: 10.1172/jci13595.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisPECAM-1-deficient miceEndothelial cellsAutoimmune encephalomyelitisVascular permeabilityDevelopment of EAET lymphocyte transendothelial migrationEarly onsetHuman autoimmune disease multiple sclerosisAutoimmune disease multiple sclerosisCell adhesion molecule-1Altered vascular permeabilityCNS vascular permeabilityMononuclear cell extravasationDisease multiple sclerosisPlatelet/endothelial cell adhesion molecule-1Wild-type miceAdhesion molecule-1Endothelial cell adhesion molecule-1Subsets of leukocytesPECAM-1 expressionLymphocyte transendothelial migrationEarly time pointsHistamine challengeMultiple sclerosisLymphocyte 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
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
1998
T helper cell differentiation in multiple sclerosis and autoimmunity
Martin R, Ruddle N, Reingold S, Hafler D. T helper cell differentiation in multiple sclerosis and autoimmunity. Trends In Immunology 1998, 19: 495-498. PMID: 9818541, DOI: 10.1016/s0167-5699(98)01345-0.Peer-Reviewed Original Research