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 ResearchMeSH KeywordsAnimalsCytokinesDendritic CellsImmunity, InnateKiller Cells, NaturalMiceSignal TransductionConceptsType 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
Commensal Microbiota Modulation of Natural Resistance to Virus Infection
Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal Microbiota Modulation of Natural Resistance to Virus Infection. Cell 2020, 183: 1312-1324.e10. PMID: 33212011, PMCID: PMC7799371, DOI: 10.1016/j.cell.2020.10.047.Peer-Reviewed Original ResearchConceptsMicrobial moleculesVesicular stomatitis virusCommensal microbesSpecific commensal microbesInduction of IFNVirus infectionNatural resistanceOuter membraneGut commensal microbesIFN-β expressionImmune system regulationHuman diseasesPhysiological importanceInduces expressionSource of IFNMicrobesHomeostatic conditionsStomatitis virusIFN-IsMicrobiota modulationAntiviral immunityCrucial mediatorIFNPolysaccharide AAntiviral activity
2019
YTHDF1 Control of Dendritic Cell Cross-Priming as a Possible Target of Cancer Immunotherapy
Kim DJ, Iwasaki A. YTHDF1 Control of Dendritic Cell Cross-Priming as a Possible Target of Cancer Immunotherapy. Biochemistry 2019, 58: 1945-1946. PMID: 30943019, DOI: 10.1021/acs.biochem.9b00200.Peer-Reviewed Original Research
2016
CD301b+ 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 IInfection
2015
Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity
Hayashi K, Sasai M, Iwasaki A. Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity. International Immunology 2015, 27: 435-445. PMID: 25925170, PMCID: PMC4560039, DOI: 10.1093/intimm/dxv021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell MembraneDendritic CellsDNA-Binding ProteinsEndosomesInterferon Type ILysosome-Associated Membrane GlycoproteinsMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesProtein TransportSignal TransductionToll-Like Receptor 7Toll-Like Receptor 9Transcription FactorsVesicle-Associated Membrane Protein 3ConceptsDifferent dendritic cell subsetsIFN inductionDendritic cell subsetsInduction of cytokinesType I IFN inductionType I IFNType I interferonI IFN inductionViral nucleic acidsAnti-viral programsTLR9 traffickingCell subsetsTLR9 signalsI IFNI interferonInhibitor treatmentDistinct subcellular membranesRAW264.7 cellsType I interferon (IFN) genesTLR9Distinct endosomal compartmentsInterferon genesTLR traffickingConfocal microscopyInductionControl of adaptive immunity by the innate immune system
Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nature Immunology 2015, 16: 343-353. PMID: 25789684, PMCID: PMC4507498, DOI: 10.1038/ni.3123.Peer-Reviewed Original ResearchCandida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation
Kashem SW, Igyártó B, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity 2015, 42: 356-366. PMID: 25680275, PMCID: PMC4343045, DOI: 10.1016/j.immuni.2015.01.008.Peer-Reviewed Original ResearchConceptsT helper cell responsesHelper cell responsesCell responsesInterleukin-6Systemic infectionDectin-1 ligationTh1 cell responsesTh cell responsesT helper 17 (Th17) cell differentiationT helper cell differentiationTissue-specific protectionSkin infection modelMurine skin infection modelC. albicansHelper cell differentiationMucocutaneous immunityCutaneous infectionsVaccine strategiesLangerhans cellsSystemic immunityT cellsCell differentiationInfection modelInfectionImmunity
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 subsetCD301bIL-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
Autophagy and selective deployment of Atg proteins in antiviral defense
Yordy B, Tal MC, Hayashi K, Arojo O, Iwasaki A. Autophagy and selective deployment of Atg proteins in antiviral defense. International Immunology 2012, 25: 1-10. PMID: 23042773, PMCID: PMC3534236, DOI: 10.1093/intimm/dxs101.Peer-Reviewed Original ResearchConceptsAutophagy machineryAtg proteinsAntiviral defenseViral pathogen-associated molecular patternsPathogen-associated molecular patternsEukaryotic cellsCellular homeostasisCanonical autophagyViral replication sitesMajor histocompatibility complex presentationIntracellular transportAntiviral proteinCytosolic componentsRegulatory functionsEndolysosomal compartmentsReplication sitesAutophagyMachineryMolecular patternsDiverse repertoireIntracellular materialProteinToll-like receptorsViral antigen processingSelective targetingInnate Immune Recognition of HIV-1
Iwasaki A. Innate Immune Recognition of HIV-1. Immunity 2012, 37: 389-398. PMID: 22999945, PMCID: PMC3578946, DOI: 10.1016/j.immuni.2012.08.011.Peer-Reviewed Original ResearchAdaptor 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
Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3
Sasai M, Linehan MM, Iwasaki A. Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3. Science 2010, 329: 1530-1534. PMID: 20847273, PMCID: PMC3063333, DOI: 10.1126/science.1187029.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAnimalsCells, CulturedCytokinesCytoplasmic VesiclesDendritic CellsEndosomesInterferon Regulatory Factor-7Interferon Type ILysosomal-Associated Membrane Protein 2MacrophagesMembrane Transport ProteinsMiceMice, Inbred C57BLMyeloid Differentiation Factor 88OligodeoxyribonucleotidesProtein TransportRecombinant Fusion ProteinsSignal TransductionTNF Receptor-Associated Factor 3Toll-Like Receptor 9Transcriptional ActivationVesicle-Associated Membrane Protein 3ConceptsI interferonTLR9 signalsEndosomal Toll-like receptors 7Toll-like receptor 9 signalingToll-like receptor 7Protein 3Type I IFNsDependent proinflammatory cytokinesInterferon regulatory factor 7I IFNsProinflammatory cytokine genesType I interferonNuclear factor κBRegulatory factor 7Viral nucleic acidsProinflammatory cytokinesReceptor 7Factor κBCytokine genesTLR9Adaptor protein 3Intracellular mechanismsFactor 7Viral pathogensReceptor traffickingCD8+ 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 IFNInfluenza virus activates inflammasomes via its intracellular M2 ion channel
Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nature Immunology 2010, 11: 404-410. PMID: 20383149, PMCID: PMC2857582, DOI: 10.1038/ni.1861.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCells, CulturedCytokinesDendritic CellsGenetic EngineeringGolgi ApparatusHydrogen-Ion ConcentrationIon ChannelsMacrophagesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMonensinNLR Family, Pyrin Domain-Containing 3 ProteinOncogene Proteins, ViralOrthomyxoviridaeOrthomyxoviridae InfectionsPotassium ChlorideProtein TransportProtonsSequence DeletionToll-Like Receptor 7Viral Matrix ProteinsVirus ReplicationIn Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells
Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, Mizushima N, Grinstein S, Iwasaki A. In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells. Immunity 2010, 32: 227-239. PMID: 20171125, PMCID: PMC2996467, DOI: 10.1016/j.immuni.2009.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutophagy-Related Protein 5Cells, CulturedDendritic CellsFemaleHerpes SimplexHerpesvirus 2, HumanHistocompatibility Antigens Class IILymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsRadiation ChimeraRNA, Small InterferingConceptsMHC-II presentationMHC class IIDendritic cellsAntigen presentationClass IIHerpes simplex virus infectionToll-like receptor stimuliT cell primingSimplex virus infectionCell primingAbsence of ATG5Microbial antigensVirus infectionMHC ICytosolic antigensConditional deletionAntigenReceptor stimuliAutophagic machineryKey autophagy genesRapid diseasePresentationATG5Lysosome fusionAutophagy genes
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