2023
Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity
Weizman O, Luyten S, Krykbaeva I, Song E, Mao T, Bosenberg M, Iwasaki A. Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity. The Journal Of Immunology 2023, 210: 1146-1155. PMID: 36881866, PMCID: PMC10067787, DOI: 10.4049/jimmunol.2200697.Peer-Reviewed Original ResearchConceptsType 2 dendritic cellsMetastatic burdenImmune circuitsDendritic cellsConventional type 2 dendritic cellsSyngeneic murine melanomaNK cell compartmentImmune cell responsesColon cancer modelEarly metastatic seedingMetastatic controlTranscription factor IRF3DC populationsNK cellsProinflammatory cytokinesNucleic acid sensingPrimary tumorEffector responsesMetastatic spreadDisease outcomeIntracardiac injectionT cellsInitial immunityTissue-specific ablationCancer model
2020
Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding
Weizman O, Krykbaeva I, Bosenburg M, Iwasaki A. Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding. The Journal Of Immunology 2020, 204: 88.17-88.17. DOI: 10.4049/jimmunol.204.supp.88.17.Peer-Reviewed Original ResearchConventional type 2 dendritic cellsType 2 dendritic cellsImmune cellsMetastatic burdenNK cellsDendritic cellsIntracardiac injectionHost anti-tumor immunityType I IFN-independent mannerAdaptive immune cellsAnti-tumor immunityLocal immune cellsNatural killer cellsSyngeneic mouse modelIFN-independent mannerEarly metastatic seedingMetastatic controlTranscription factor IRF3Killer cellsPrimary tumorMetastatic spreadInnate sensorsMouse modelMetastatic growthMetastatic seeding
2019
Antigen 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
2018
Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner
Gopinath S, Kim MV, Rakib T, Wong PW, van Zandt M, Barry NA, Kaisho T, Goodman AL, Iwasaki A. Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner. Nature Microbiology 2018, 3: 611-621. PMID: 29632368, PMCID: PMC5918160, DOI: 10.1038/s41564-018-0138-2.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, TopicalAminoglycosidesAnimalsAnti-Bacterial AgentsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGerm-Free LifeHumansInfluenza A virusMiceMicrobiotaOligonucleotide Array Sequence AnalysisSimplexvirusToll-Like Receptor 3Transcription FactorsVirus DiseasesVirus ReplicationZika VirusConceptsToll-like receptor 3Aminoglycoside treatmentInterferon-stimulated genesViral infectionReceptor 3ISG inductionAminoglycoside antibioticsMicrobiota-independent mannerGerm-free miceAdapter-inducing interferonInterferon regulatory factor 3Herpes simplex virusTopical mucosal applicationRegulatory factor 3Dendritic cellsAntibiotic useAntiviral effectAminoglycoside applicationHost resistanceSimplex virusAntiviral resistanceVaginal mucosaMarked upregulationMucosal applicationTopical application
2017
RAB15 empowers dendritic cells to drive antiviral immunity
Wong P, Iwasaki A. RAB15 empowers dendritic cells to drive antiviral immunity. Science Immunology 2017, 2: eaan6448. PMID: 28783705, DOI: 10.1126/sciimmunol.aan6448.Peer-Reviewed Original Research
2016
Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in Mice
Gibb D, Natarajan P, Liu J, Santhanakrishnan M, Iwasaki A, Hendrickson J. Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in Mice. Blood 2016, 128: 19. DOI: 10.1182/blood.v128.22.19.19.Peer-Reviewed Original ResearchMonocyte-derived dendritic cellsReactivity of seraPeak antibody responseWT miceIfnar1-/- miceType 1 interferonDendritic cellsRBC transfusionPeripheral bloodAntibody responseRBC alloimmunizationAlloimmune responseSpecific IgGIgG antibodiesInflammatory diseasesMouse modelRBC antigensIndividual miceCCR2-/- miceFrequency of alloimmunizationHuman KEL glycoproteinFlow cytometric crossmatchActivation marker expressionDendritic cell activationRole of inflammationEarly local immune defences in the respiratory tract
Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nature Reviews Immunology 2016, 17: 7-20. PMID: 27890913, PMCID: PMC5480291, DOI: 10.1038/nri.2016.117.Peer-Reviewed Original ResearchConceptsRespiratory tractImmune responseDendritic cellsType 2 immune responsesType 1 immune responsePlasmacytoid dendritic cellsEpithelial cellsTissue-resident lymphocytesLower respiratory tractType of infectionUpper respiratory tractAirway epithelial cellsLocal immune defensePattern recognition receptorsAntimicrobial host defenseLymphoid cell typesCell typesRespiratory infectionsEffector cellsSecrete cytokinesAllergen resultsInnate sensorsMast cellsAirway cellsPathological inflammationCD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2
Shin H, Kumamoto Y, Gopinath S, Iwasaki A. CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2. Nature Communications 2016, 7: 13346. PMID: 27827367, PMCID: PMC5105190, DOI: 10.1038/ncomms13346.Peer-Reviewed Original ResearchConceptsCD8 TRM cellsAntigen-presenting cellsGenital HSV-2 infectionTissue-resident memory CD8HSV-2 infectionTRM cellsDendritic cellsMemory CD8Protective immunityT cellsPopulations of APCsGenital HSV-2Protective immune responseFemale genital tractMHC class IHSV-2Genital tractAntigen presentationImmune responseLamina propriaViral infectionConfer protectionBarrier tissuesClass IInfectionCD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens
Kumamoto Y, Hirai T, Wong PW, Kaplan DH, Iwasaki A. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. ELife 2016, 5: e17979. PMID: 27657168, PMCID: PMC5033605, DOI: 10.7554/elife.17979.Peer-Reviewed Original ResearchDendritic cellsAntibody responsePD-L1Protein antigensBlocking PD-1Follicular helper cellsPD-1 ligandsStrong antibody responseWild-type miceGerminal center B cellsTfh cellsPD-1Cell primingIgG responsesHelper cellsPD-L2Autoantibody generationSuccessful vaccineCD301bB cellsTransient depletionAntigenMiceAntibodiesNovel regulatory mechanismAXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
Schmid ET, Pang IK, Silva E, Bosurgi L, Miner JJ, Diamond MS, Iwasaki A, Rothlin CV. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. ELife 2016, 5: e12414. PMID: 27350258, PMCID: PMC4924996, DOI: 10.7554/elife.12414.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonDendritic cellsIL-1βAntiviral T cell immunityAntiviral adaptive immunityPotent immunosuppressive functionT cell immunityT cell primingInhibition of AXLType I IFN receptorAxl receptor tyrosine kinaseReceptor tyrosine kinase AXLControl of infectionType I interferonI IFN receptorTyrosine kinase AXLDC maturationCell immunityWest Nile virusCell primingImmunosuppressive functionImmunosuppressive effectsAdaptive immunity
2014
Innate immunity to influenza virus infection
Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nature Reviews Immunology 2014, 14: 315-328. PMID: 24762827, PMCID: PMC4104278, DOI: 10.1038/nri3665.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionToll-like receptor 7T cell responsesVirus infectionInterferon-stimulated genesIL-1βNLRP3 inflammasomeViral challengeB cellsCell responsesHigh-dose viral challengeInfluenza virusAntiviral B cellsMultiple pattern recognition receptorsPlasmacytoid dendritic cellsAdaptive immune responsesInfected cellsRetinoic acid-inducible gene IAirway epithelial cellsAcid-inducible gene IPattern recognition receptorsInfluenza virus-infected cellsVirus-infected cellsAntiviral defense genesDendritic 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 subsetCD301bInnate immunity
Iwasaki A, Peiris M. Innate immunity. 2013, 267-282. DOI: 10.1002/9781118636817.ch17.Peer-Reviewed Original ResearchToll-like receptorsNOD-like receptorsImmune responseVirus infectionInfluenza virusHundreds of IFNProtective host responseInfluenza virus infectionAdaptive immune responsesInnate immune responseType I IFNInfluenza virus replicationInnate immune systemDendritic cellsNK cellsInfluenza infectionIL-1βInnate sensorsAdaptive immunityLike receptorsDetrimental pathologyI IFNAlveolar macrophagesHost responseImmune systemIL-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 7Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses
Mattei LM, Cotmore SF, Li L, Tattersall P, Iwasaki A. Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses. Journal Of Virology 2013, 87: 3605-3608. PMID: 23302877, PMCID: PMC3592163, DOI: 10.1128/jvi.03155-12.Peer-Reviewed Original Research
2012
Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes
Henault J, Martinez J, Riggs JM, Tian J, Mehta P, Clarke L, Sasai M, Latz E, Brinkmann MM, Iwasaki A, Coyle AJ, Kolbeck R, Green DR, Sanjuan MA. Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes. Immunity 2012, 37: 986-997. PMID: 23219390, PMCID: PMC3786711, DOI: 10.1016/j.immuni.2012.09.014.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Adaptor protein 3Plasmacytoid dendritic cellsDNA-containing immune complexesI interferonPathogenic DNAMicrotubule-associated proteinsType I interferon secretionIFN-α productionDNA immune complexesPreinitiation complexType I interferonAnti-DNA autoantibodiesNoncanonical autophagyAutophagic pathwayHost DNADendritic cellsAutoimmune disordersReceptor 9Interferon secretionChain 3Immune complexesProtein 3DNAInterferonAdaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells
Mantegazza AR, Guttentag SH, El-Benna J, Sasai M, Iwasaki A, Shen H, Laufer TM, Marks MS. Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells. Immunity 2012, 36: 782-794. PMID: 22560444, PMCID: PMC3361531, DOI: 10.1016/j.immuni.2012.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3AnimalsAntigen PresentationAntigensCD4-Positive T-LymphocytesCell DifferentiationCell MembraneCells, CulturedDendritic CellsEndocytosisHistocompatibility Antigens Class IILigandsListeria monocytogenesListeriosisMiceMice, Inbred C57BLMice, TransgenicMyeloid Differentiation Factor 88OvalbuminPeptidesPhagocytosisPhagosomesSignal TransductionTh1 CellsToll-Like ReceptorsConceptsToll-like receptor signalingDendritic cellsAntigen presentationAdaptor protein 3Protein 3Receptor signalingMHC-II presentationEffector cell functionListeria monocytogenes infectionTLR ligandsMonocytogenes infectionTLR4 recruitmentT cellsCell activationIntracellular storesPhagolysosome maturationCell functionPearl miceReceptor-mediated endocytosisAntigenPresentationMolecular mechanismsPhagosomesCell surfaceSignaling
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
2010
Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue
Iijima N, Mattei LM, Iwasaki A. Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 108: 284-289. PMID: 21173243, PMCID: PMC3017177, DOI: 10.1073/pnas.1005201108.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell DifferentiationCytokinesEnzyme-Linked Immunospot AssayFemaleFluorescein-5-isothiocyanateHerpes GenitalisHerpesvirus 2, HumanInterferon-gammaMiceMice, Inbred C57BLMice, KnockoutMonocytesReceptor, Interferon alpha-betaReceptors, CCR2Th1 CellsConceptsMonocyte-derived APCTh1 immunityInflammatory monocytesTh1 cellsCD4 T cell primingHerpes simplex virus 2Effector Th1 cellsMemory Th1 cellsPrimary mucosal infectionSecondary viral challengeT cell primingIFN-γ secretionSimplex virus 2Signs of infectionImportance of monocytesAPC subsetsCell primingDendritic cellsMucosal infectionsViral challengePeripheral tissuesMucosal tissuesAntiviral protectionMonocytesInfection