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 cellsAutoimmunityLymphotoxin 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
2019
Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
Camell CD, Günther P, Lee A, Goldberg EL, Spadaro O, Youm YH, Bartke A, Hubbard GB, Ikeno Y, Ruddle NH, Schultze J, Dixit VD. Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metabolism 2019, 30: 1024-1039.e6. PMID: 31735593, PMCID: PMC6944439, DOI: 10.1016/j.cmet.2019.10.006.Peer-Reviewed Original ResearchConceptsAge-associated B cellsFat-associated lymphoid clustersB cellsAdipose tissue leukocytesB-cell depletionB cell accumulationBody temperature maintenanceFALC formationVisceral adiposityCell depletionNLRP3 inflammasomeFemale miceLymphoid clustersMetabolic dysfunctionIL-1Metabolic impairmentIL-1RTissue leukocytesCell accumulationMetabolic homeostasisUnique populationLipolysisCellsTemperature maintenanceAdiposity
2016
Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis
Chia JJ, Zhu T, Chyou S, Dasoveanu DC, Carballo C, Tian S, Magro CM, Rodeo S, Spiera RF, Ruddle NH, McGraw TE, Browning JL, Lafyatis R, Gordon JK, Lu TT. Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis. Journal Of Clinical Investigation 2016, 126: 4331-4345. PMID: 27721238, PMCID: PMC5096920, DOI: 10.1172/jci85740.Peer-Reviewed Original ResearchConceptsAdipose-derived mesenchymal stromal cellsDendritic cellsSkin fibrosisDermal white adipose tissueFibrotic skinAdipose tissueStromal cellsMesenchymal stromal cell therapyScleroderma skin fibrosisStromal cell therapyWhite adipose tissueAdipose-derived stromal cellsMesenchymal stromal cellsΒ expressionMurine modelEffective treatmentFibrosisΒ1-integrin pathwayReparative functionsCell therapySclerodermaSkin functionIntegrin pathwaySurvivalAtrophyThe 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
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
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 ResearchPillars 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 ResearchCell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation
Paul D, Ge S, Lemire Y, Jellison ER, Serwanski DR, Ruddle NH, Pachter JS. Cell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation. Journal Of Neuroinflammation 2014, 11: 10. PMID: 24444311, PMCID: PMC3906899, DOI: 10.1186/1742-2094-11-10.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisBlood-brain barrierCentral nervous systemBrain microvascular endothelial cellsKO miceEarly experimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoprotein peptideEndothelial cellsNormal central nervous systemReduced EAE severityClinical disease progressionIFN-γ productionT cell proliferationWild-type miceMicrovascular endothelial cellsCCL2 immunoreactivityEAE severityImmunofluorescence confocal microscopyBBB damageEAE modelAutoimmune encephalomyelitisIL-17Neuroinflammatory conditionsNeuroinflammatory diseasesWT mice
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
Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
Kuerten S, Schickel A, Kerkloh C, Recks MS, Addicks K, Ruddle NH, Lehmann PV. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response. Acta Neuropathologica 2012, 124: 861-873. PMID: 22842876, DOI: 10.1007/s00401-012-1023-3.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsExperimental autoimmune encephalomyelitisMyelin-specific T cell responseCentral nervous systemB cell aggregatesT cell responsesMultiple sclerosisB cell aggregationDeterminant spreadingB cellsCell responsesActive immune responseMyelin basic proteinLymphoid neogenesisAutoimmune encephalomyelitisMS patientsAggressive diseaseAutoimmune pathologyPatient populationLymphoid organsDisease onsetDisease progressionT cellsImmune responsePathogenic contributionA 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 AcidProxTom 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
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 mechanismsBlocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses
Motallebzadeh R, Rehakova S, Conlon TM, Win TS, Callaghan CJ, Goddard M, Bolton EM, Ruddle NH, Bradley JA, Pettigrew GJ. Blocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses. The FASEB Journal 2011, 26: 51-62. PMID: 21926237, DOI: 10.1096/fj.11-186973.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBone MarrowCD4-Positive T-LymphocytesChoristomaChronic DiseaseGraft RejectionHeart TransplantationIsoantibodiesLymphoid TissueLymphotoxin beta ReceptorLymphotoxin-betaMiceMice, Inbred C57BLMice, KnockoutMyocardiumNeovascularization, PathologicRecombinant Fusion ProteinsSignal TransductionSpleenTransplantation, HomologousConceptsTertiary lymphoid organsCardiac allograftsHeart allograftsB cellsLymphotoxin β receptor (LTβR) signalingEctopic lymphoid tissueGerminal center activityLTβR-IgTLO formationPostoperative administrationAccelerated rejectionHumoral autoimmunityAlloimmune responseAutoantibody productionAutoantibody responseHumoral responseLymphoid organsLymphoid tissueLymphoid organogenesisEffector antibodiesMouse modelAllograftsTransplantationAutoantibodiesCellsResident B cells regulate thymic expression of myelin oligodendrocyte glycoprotein
Akirav EM, Xu Y, Ruddle NH. Resident B cells regulate thymic expression of myelin oligodendrocyte glycoprotein. Journal Of Neuroimmunology 2011, 235: 33-39. PMID: 21550671, PMCID: PMC3157307, DOI: 10.1016/j.jneuroim.2011.03.013.Peer-Reviewed Original ResearchConceptsB cellsB cell-deficient μMT miceMyelin oligodendrocyte glycoproteinResident B cellsThymic B cellsCortico-medullary junctionMinor cell populationProduction of LTInsulin mRNA expressionΜMT miceEpithelial cell numberOligodendrocyte glycoproteinThymic expressionAntigen expressionMRNA expressionNormal tissuesCell populationsCell numberCellsExpressionLtUnexpected roleBiological roleLymphotoxinMice