2020
VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice
Pi R, Iwasaki A, Sewald X, Mothes W, Uchil PD. Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00930-19. PMID: 31434732, PMCID: PMC6803250, DOI: 10.1128/jvi.00930-19.Peer-Reviewed Original ResearchConceptsPopliteal lymph nodesFriend murine leukemia virusInnate immune sensing pathwaysToll-like receptor 7Viral spreadMurine leukemia virusCell-deficient miceType I interferon responseWild-type miceCell populationsType I interferonLeukemia virusRobust virus replicationI interferon responseAntiviral intervention strategiesInfected cell typesSentinel macrophagesAdoptive transferCell typesLymph nodesReceptor 7Virus infectionInnate sensingB cellsI interferon
2013
Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response
Sellers SL, Iwasaki A, Payne GW. Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response. PLOS ONE 2013, 8: e60741. PMID: 23573281, PMCID: PMC3616017, DOI: 10.1371/journal.pone.0060741.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsArteriolesCell DegranulationChlorocebus aethiopsFemaleHerpes SimplexLymph NodesMast CellsMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNifedipineNitric OxideNitric Oxide Synthase Type IIIPhenylephrineTumor Necrosis Factor-alphaVasoconstrictionVasodilator AgentsVero CellsConceptsAdaptive immune responsesEndothelial nitric oxide synthaseImmune responseVascular remodelingHerpes simplex type II infectionT cell-dependent mechanismGenetic ablation modelCell-dependent mechanismNitric oxide levelsType II infectionNitric oxide synthaseCourse of infectionInguinal LNsLN cellularityVascular eventsVascular changesArteriole diameterPharmacological blockadeMain arterioleOxide synthaseTNFα expressionMast cellsOxide levelsViral infectionIntravital microscopy
2011
CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input
Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A. CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8749-8754. PMID: 21555577, PMCID: PMC3102372, DOI: 10.1073/pnas.1100567108.Peer-Reviewed Original ResearchConceptsT cellsDendritic cellsCytotoxic T-lymphocyte primingT lymphocyte responsesAntigen-specific CTLsT lymphocyte primingSecondary lymphoid organsT cell helpCD40-dependent mannerNaïve B cellsCognate CTLsAcute infectionLymph nodesLymphocyte primingLymphocyte responsesLymphocyte recruitmentCTL expansionLymphoid organsImmune responseNaïve precursorsB cellsImmune systemReactive LNsIntracellular pathogensInfection
2010
CD8+ T Cell Responses following Replication-Defective Adenovirus Serotype 5 Immunization Are Dependent on CD11c+ Dendritic Cells but Show Redundancy in Their Requirement of TLR and Nucleotide-Binding Oligomerization Domain-Like Receptor Signaling
Lindsay RW, Darrah PA, Quinn KM, Wille-Reece U, Mattei LM, Iwasaki A, Kasturi SP, Pulendran B, Gall JG, Spies AG, Seder RA. CD8+ T Cell Responses following Replication-Defective Adenovirus Serotype 5 Immunization Are Dependent on CD11c+ Dendritic Cells but Show Redundancy in Their Requirement of TLR and Nucleotide-Binding Oligomerization Domain-Like Receptor Signaling. The Journal Of Immunology 2010, 185: 1513-1521. PMID: 20610651, DOI: 10.4049/jimmunol.1000338.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviruses, HumanAnimalsAntigen PresentationCD11c AntigenCD8-Positive T-LymphocytesDefective VirusesDendritic CellsImmunity, InnateImmunophenotypingInterferon Type IInterleukin-12Intracellular Signaling Peptides and ProteinsLymph NodesMiceMice, Inbred C57BLMice, KnockoutOligodeoxyribonucleotidesSignal TransductionToll-Like ReceptorsViral VaccinesVirionConceptsT cell responsesCD8 T cell responsesDendritic cellsCell responsesRAd5 immunizationCD8 responsesDC subsetsInnate cytokinesOligomerization domain-like receptor protein 3Domain-like receptor protein 3OT-I CD8 T cellsCD4 T cell responsesCD8 T cell proliferationNucleotide-Binding Oligomerization DomainReplication-defective adenovirus serotype 5Plasmacytoid dendritic cellsReceptor protein 3CD8 T cellsDistinct DC subsetsT cell immunityApoptosis-associated speck-like proteinPre-existing immunityT cell proliferationLike receptor signalingType I IFN
2008
Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node
Thompson JM, Nicholson MG, Whitmore AC, Zamora M, West A, Iwasaki A, Staats HF, Johnston RE. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node. The Journal Of Immunology 2008, 181: 574-585. PMID: 18566424, PMCID: PMC3603373, DOI: 10.4049/jimmunol.181.1.574.Peer-Reviewed Original ResearchConceptsDraining Lymph NodesVirus replicon particlesMucosal immune responsesMucosal lymphoid tissuesImmune inductionAg deliveryIgA AbsLymph nodesLymphoid tissueImmune responseMucosal surfacesMucosal addressin cell adhesion molecule-1Strong mucosal immune responsesEncephalitis virus replicon particlesCell adhesion molecule-1Multiple mucosal surfacesViral-based vaccinesAdhesion molecule-1Lymphoid structuresIL-6Immunological parametersImmunological componentsCC chemokinesIgA detectionReplicon particles
2007
Vaginal epithelial dendritic cells renew from bone marrow precursors
Iijima N, Linehan MM, Saeland S, Iwasaki A. Vaginal epithelial dendritic cells renew from bone marrow precursors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 19061-19066. PMID: 18006657, PMCID: PMC2141908, DOI: 10.1073/pnas.0707179104.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAnimals, CongenicAntigens, CDAntigens, SurfaceBone Marrow CellsCell LineageDiestrusEpidermal CellsEpithelial CellsFemaleHerpes GenitalisLectins, C-TypeLymph NodesMannose-Binding LectinsMiceMice, Inbred C57BLMice, TransgenicMucous MembraneMultipotent Stem CellsOrgan SpecificityRadiation ChimeraVaginaConceptsEpithelial dendritic cellsDendritic cellsLangerhans cellsKey professional antigen-presenting cellsProfessional antigen-presenting cellsSkin Langerhans cellsAntigen-presenting cellsPrimary immune responseEpidermal Langerhans cellsMucosal epithelial liningBone marrow precursorsSquamous epithelial layerStratified squamous epithelial layerHSV-2Sex hormonesImmune responseOral cavityVaginal mucosaEpithelial liningMarrow precursorsActivation statusSpecialized subsetCytometric analysisEpithelial layerCells
2005
Innate control of adaptive immunity via remodeling of lymph node feed arteriole
Soderberg KA, Payne GW, Sato A, Medzhitov R, Segal SS, Iwasaki A. Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 16315-16320. PMID: 16260739, PMCID: PMC1283434, DOI: 10.1073/pnas.0506190102.Peer-Reviewed Original ResearchConceptsLymph nodesNaïve lymphocytesAdaptive immunityInnate controlFeed arteriolesLocal lymph nodesSecondary lymphoid organsAntigen-specific stimulationInnate immune recognitionAntigen-specific lymphocytesPathogen-derived antigensAdaptive immune systemCognate lymphocytesLymphocyte recruitmentLymphoid organsForeign antigensImmune recognitionImmune systemCognate antigenLymphocytesVascular inputRare antigen-specific lymphocytesAntigenArteriolesImmunity
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
2000
Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells
Gurunathan S, Stobie L, Prussin C, Sacks D, Glaichenhaus N, Iwasaki A, Fowell D, Locksley R, Chang J, Wu C, Seder R. Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells. The Journal Of Immunology 2000, 165: 915-924. PMID: 10878366, DOI: 10.4049/jimmunol.165.2.915.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ProtozoanCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8 AntigensCD8-Positive T-LymphocytesCell DivisionCells, CulturedDNA, ProtozoanGenes, T-Cell Receptor betaImmune SeraImmunity, CellularInjections, SubcutaneousInterferon-gammaInterleukin-12Leishmania majorLeishmaniasis, CutaneousLymph NodesLymphocyte ActivationMiceMice, Inbred BALB CMice, TransgenicProtein Kinase CProtozoan ProteinsReceptors, InterleukinReceptors, Interleukin-12Th1 CellsVaccines, DNAConceptsIFN-gamma-producing T cellsDepletion of CD8DNA-vaccinated miceT cellsDNA vaccinationProtective immunityImmunoregulatory roleWk postvaccinationLong-term protective immunityLACK-specific CD4Time of vaccinationPotential immunoregulatory roleNovel immunoregulatory roleTh1 immunityIL-12Th1 cellsInfectious challengeCD8VaccinationInfectionLeishmania majorStriking decreaseMiceImmunityPostvaccinationPrimary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses
He J, Gurunathan S, Iwasaki A, Ash-Shaheed B, Kelsall B. Primary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses. Journal Of Experimental Medicine 2000, 191: 1605-1610. PMID: 10790434, PMCID: PMC2213427, DOI: 10.1084/jem.191.9.1605.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCD8 AntigensCell DifferentiationDendritic CellsGTP-Binding Protein alpha Subunits, Gi-GoInterferon-gammaInterleukin-10Interleukin-12Interleukin-4Leishmaniasis, CutaneousLymph NodesMiceMice, Inbred BALB CMice, Mutant StrainsPertussis ToxinProtein Processing, Post-TranslationalSignal TransductionSpleenTh1 CellsTumor Necrosis Factor-alphaVirulence Factors, BordetellaConceptsPertussis toxinGi-protein signalingTh1 responseIL-12T helper cell type 1 responseGi proteinsNormal BALB/c miceBALB/c miceLymphoid dendritic cellsIL-12 productionInterleukin-12 productionType 1 responseCapacity of splenocytesIL-12 p40Tumor necrosis factorRegulation of interleukinT cell differentiationNonmicrobial stimuliDendritic cellsIL-10Lymph nodesC miceTNF-alphaNecrosis factorProtein signaling