2024
Compartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signal
2023
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
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 interferonAntigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate
Tatsumi N, Iwasaki A, Kumamoto Y. Antigen presentation by CD301b+ dermal dendritic cells dictates CD4+ T cell fate. The Journal Of Immunology 2019, 202: 56.9-56.9. DOI: 10.4049/jimmunol.202.supp.56.9.Peer-Reviewed Original ResearchCD4 T cellsOT-II cellsAntigen-specific CD4 T cellsDermal dendritic cellsDendritic cellsMHC class IIT cellsTh2 differentiationAntigen presentationCognate interactionPolyclonal CD4T cellsT cells 7 daysEffector CD4 T cellsT helper type 2 cellsMajor DC subsetsIL-4 productionEpidermal Langerhans cellsCells 7 daysType 2 cellsDC subsetsT cell fateLymph nodesOverall cell cycle progressionLangerhans cellsTh2 cells
2013
CD301b+ Dermal Dendritic Cells Drive T Helper 2 Cell-Mediated Immunity
Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A. CD301b+ Dermal Dendritic Cells Drive T Helper 2 Cell-Mediated Immunity. Immunity 2013, 39: 733-743. PMID: 24076051, PMCID: PMC3819035, DOI: 10.1016/j.immuni.2013.08.029.Peer-Reviewed Original ResearchConceptsDermal dendritic cellsDendritic cellsDermal DCsTh2 cellsT cellsT helper 2 cellsT helper responsesInterleukin-4 productionExpression of CD69Th2 cell developmentDC depletionLymph nodesTh2 immunityHelper responsesSubcutaneous immunizationNippostrongylus brasiliensisKey mediatorTransient depletionCell developmentImmunityOvalbuminDepletion approachCellsParticular subsetCD301b
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 pathogensInfectionMicrobiota regulates immune defense against respiratory tract influenza A virus infection
Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 5354-5359. PMID: 21402903, PMCID: PMC3069176, DOI: 10.1073/pnas.1019378108.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionVirus infectionDendritic cellsImmune responseCommensal bacteriaRespiratory influenza virus infectionToll-like receptor ligandsVirus-specific CD4CD8 T cellsT cell primingCommensal microbiota compositionProductive immune responseExpression of mRNADistal injectionLymph nodesImmune impairmentIntact microbiotaIL-1βAntibody responseImmune homeostasisRespiratory mucosaAntibiotic treatmentT cellsInflammasome activationCommensal microbiota
2009
Regulation of Immature Dendritic Cell Migration by RhoA Guanine Nucleotide Exchange Factor Arhgef5*
Wang Z, Kumamoto Y, Wang P, Gan X, Lehmann D, Smrcka AV, Cohn L, Iwasaki A, Li L, Wu D. Regulation of Immature Dendritic Cell Migration by RhoA Guanine Nucleotide Exchange Factor Arhgef5*. Journal Of Biological Chemistry 2009, 284: 28599-28606. PMID: 19713215, PMCID: PMC2781403, DOI: 10.1074/jbc.m109.047282.Peer-Reviewed Original ResearchConceptsDendritic cellsBone marrow-derived mature dendritic cellsMigration of DCsAllergic airway inflammationImmature dendritic cellsMature dendritic cellsDendritic cell migrationRAW264.7 cell lineHuman embryonic kidney 293 cellsAirway inflammationShort hairpin RNALymph nodesEmbryonic kidney 293 cellsB lymphocytesActivation of RhoALeukocyte chemotaxisKidney 293 cellsMouse linesMouse macrophagesHairpin RNACell linesVivo roleCell migrationChemotaxisARHGEF5
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
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
2003
Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
Zhao X, Deak E, Soderberg K, Linehan M, Spezzano D, Zhu J, Knipe DM, Iwasaki A. Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2. Journal Of Experimental Medicine 2003, 197: 153-162. PMID: 12538655, PMCID: PMC2193810, DOI: 10.1084/jem.20021109.Peer-Reviewed Original ResearchConceptsSubmucosal dendritic cellsDendritic cellsLymph nodesHSV-2T cellsIFNgamma secretionLangerhans cellsVaginal mucosaHerpes simplex virus type 2 infectionSimplex virus type 2 infectionViral peptidesProtective Th1 immune responseVirus type 2 infectionHerpes simplex virus 2Genital mucosal surfacesHSV-2 infectionProtective Th1 responseTh1 immune responseMHC class II moleculesProtective Th1 immunityAntigen-presenting cellsType 2 infectionSimplex virus 2Class II moleculesDC populations
2000
Primary 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