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
Migrant memory B cells secrete luminal antibody in the vagina
Oh JE, Iijima N, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A. Migrant memory B cells secrete luminal antibody in the vagina. Nature 2019, 571: 122-126. PMID: 31189952, PMCID: PMC6609483, DOI: 10.1038/s41586-019-1285-1.Peer-Reviewed Original ResearchConceptsMemory B cellsFemale reproductive tractB cellsPlasma cellsReproductive tractCD4 tissue-resident memory T cellsTissue-resident memory T cellsLower female reproductive tractHerpes simplex virus 2Genital herpes infectionMemory T cellsExpression of chemokinesSimplex virus 2CXCR3-dependent mannerLocal plasma cellsLuminal antibodyMucosal antibodiesHerpes infectionPrimary infectionMucosal barrierSecondary challengeVariety of pathogensT cellsLamina propriaInducible source
2013
Tissue‐resident memory T cells
Shin H, Iwasaki A. Tissue‐resident memory T cells. Immunological Reviews 2013, 255: 165-181. PMID: 23947354, PMCID: PMC3748618, DOI: 10.1111/imr.12087.Peer-Reviewed Original ResearchConceptsMemory T cellsHuman immunodeficiency virusHerpes simplex virusGenital tractT cellsPeripheral tissuesImmune systemTissue-resident memory T cellsMemory T cell migrationTissue-resident memory cellsT cell-based vaccinesMemory T cell populationsMemory T cell subsetsAntibody-based vaccinesT cell recruitmentT cell subsetsNew vaccination strategiesT cell populationsSecondary lymphoid organsNon-lymphoid tissuesPortal of entryT cell migrationAdaptive immune systemTRM cellsEffector memoryIL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus
Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus. Nature Immunology 2013, 14: 246-253. PMID: 23314004, PMCID: PMC3577947, DOI: 10.1038/ni.2514.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell MovementDendritic CellsInfluenza A virusInterleukin-1Lymphocyte ActivationMembrane GlycoproteinsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Nerve Tissue ProteinsOrthomyxoviridae InfectionsReceptors, CCR7Receptors, Cell SurfaceReceptors, Interleukin-1Receptors, Pattern RecognitionSignal TransductionToll-Like Receptor 7
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
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 migrationChemotaxisARHGEF5Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection
Lee HK, Zamora M, Linehan MM, Iijima N, Gonzalez D, Haberman A, Iwasaki A. Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. Journal Of Experimental Medicine 2009, 206: 359-370. PMID: 19153243, PMCID: PMC2646574, DOI: 10.1084/jem.20080601.Peer-Reviewed Original ResearchConceptsResident dendritic cellsCD8 T cellsDendritic cellsHSV-1 infectionT cellsEpicutaneous infectionAntigen presentationLymph node-resident dendritic cellsHSV-specific T cellsCD4 T cell responsesNeedle injectionHerpes simplex virus 1 (HSV-1) infectionSimplex virus 1 infectionT cell primingT cell responsesVirus-1 infectionMode of infectionDC populationsCell primingVaginal infectionsImmune responseMucosal tissuesMucosal surfacesHSV-1Cell responsesInflammasome recognition of influenza virus is essential for adaptive immune responses
Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. Journal Of Experimental Medicine 2009, 206: 79-87. PMID: 19139171, PMCID: PMC2626661, DOI: 10.1084/jem.20081667.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationApoptosis Regulatory ProteinsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell MovementCytoskeletal ProteinsDendritic CellsImmunity, CellularImmunity, InnateImmunoglobulin IsotypesInterleukin-1betaLungMacrophages, AlveolarMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesNasal Lavage FluidNLR Family, Pyrin Domain-Containing 3 ProteinOrthomyxoviridaeOrthomyxoviridae InfectionsReceptors, Interleukin-1Survival AnalysisConceptsInfluenza virus infectionNOD-like receptorsInfluenza virusVirus infectionAdaptive immunityInflammasome activationRetinoic acid-inducible gene I.CD8 T cell responsesCaspase-1Influenza virus resultsMucosal IgA secretionProtective antiviral immunitySystemic IgG responseCD4 T cellsT cell responsesAdaptive immune responsesType I interferonInnate immune systemRespiratory infectionsIgG responsesProtective immunityTLR signalsIgA secretionReceptor 7T cells
2006
Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ
Lund JM, Linehan MM, Iijima N, Iwasaki A. Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ. The Journal Of Immunology 2006, 177: 7510-7514. PMID: 17114418, DOI: 10.4049/jimmunol.177.11.7510.Peer-Reviewed Original ResearchConceptsMucosal viral infectionsPlasmacytoid dendritic cellsPlasmacytoid DCsDendritic cellsViral infectionGenital HSV-2 infectionHSV-2 infectionLocal viral replicationAntiviral effector cellsInnate immune protectionTLR9-dependent mannerType I IFNsType I IFNPeripheral mucosaPowerful APCsTh1 immunityEffector cellsImmune protectionNaive lymphocytesAdaptive immunityI IFNsI IFNVaginal mucosaViral replicationInnate defense
2004
Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
Sato A, Iwasaki A. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 16274-16279. PMID: 15534227, PMCID: PMC528964, DOI: 10.1073/pnas.0406268101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationCaspase 1Cell DifferentiationCell MovementDendritic CellsFemaleHerpesvirus 2, HumanImmunity, InnateInterleukin-12Membrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicReceptors, InterferonSignal TransductionStromal CellsTh1 CellsToll-Like ReceptorsConceptsToll-like receptorsT cell responsesPattern recognition receptorsViral infectionContribution of TLRsRecognition receptorsCell responsesEffector T cell responsesHerpes simplex virus type 2Simplex virus type 2Antiviral adaptive immunityDendritic cell compartmentEffector T cellsDendritic cell maturationMost viral infectionsVirus type 2Infected epithelial cellsMucosal infectionsT cellsAdaptive immunityAntiviral immunityInfectious agentsType 2Immune recognitionStromal cellsToll-like receptor control of the adaptive immune responses
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nature Immunology 2004, 5: 987-995. PMID: 15454922, DOI: 10.1038/ni1112.Peer-Reviewed Original ResearchConceptsToll-like receptorsAdaptive immune responsesImmune responseMechanisms of TLRToll-like receptor controlHost defense responsesDendritic cell functionDendritic cell populationsMicrobial infectionsInnate immune systemDistinct anatomical locationsInflammatory reactionAdaptive immunityImmune systemAnatomical locationReceptor controlCell functionCell populationsMultiple mechanismsInfectionRecent studiesResponseInitiationSystemic defenseImportant clues
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
2002
The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo
Park MK, Amichay D, Love P, Wick E, Liao F, Grinberg A, Rabin RL, Zhang HH, Gebeyehu S, Wright TM, Iwasaki A, Weng Y, DeMartino JA, Elkins KL, Farber JM. The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo. The Journal Of Immunology 2002, 169: 1433-1443. PMID: 12133969, DOI: 10.4049/jimmunol.169.3.1433.Peer-Reviewed Original ResearchConceptsT cellsActivated B cellsB cellsDendritic cellsIFN-gammaIntracellular bacterium Francisella tularensis live vaccine strainChemotactic factorsCell activationFrancisella tularensis live vaccine strainRole of MIGT cell infiltrationTularensis live vaccine strainOptimal humoral responsesLive vaccine strainT cell activationB cell activationHuman T cellsReceptor CXCR3Humoral responseCell infiltrationLymphoid organsTarget lymphocytesCXC chemokinesInflammatory reactionPeripheral tissues