2022
Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion
Vora SM, Fontana P, Mao T, Leger V, Zhang Y, Fu TM, Lieberman J, Gehrke L, Shi M, Wang L, Iwasaki A, Wu H. Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2117198119. PMID: 35149555, PMCID: PMC8892331, DOI: 10.1073/pnas.2117198119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 nonstructural protein 1Host protein synthesisSARS-CoV-2 5Nonstructural protein 1Viral translationNucleic acid antisenseAntiviral immunityProtein synthesisTherapeutic targetTransgenic miceViral protein synthesisViral replicationDrug resistanceHuman ACE2Infected cellsProtein 1COVID-19Virulence mechanismsNanomolar concentrationsHost translationPathogenic virusesEntry channelSuppressionTranslational suppression
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
2019
Low ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virusThe Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer
Lee JW, Zhang Y, Eoh KJ, Sharma R, Sanmamed MF, Wu J, Choi J, Park HS, Iwasaki A, Kaftan E, Chen L, Papadimitrakopoulou V, Herbst RS, Koo JS. The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 1046-1060. PMID: 30771521, PMCID: PMC6542636, DOI: 10.1016/j.jtho.2019.02.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenDrug SynergismFemaleLung NeoplasmsMAP Kinase Kinase KinasesMiceMice, KnockoutMice, TransgenicMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonesSurvival AnalysisTumor Suppressor Protein p53ConceptsImmune cell populationsLung tumorsMEK inhibitorsDeath-1Survival outcomesLung cancerL1 mAbsTumor-infiltrating immune cell populationsTumor-infiltrating immune cellsCell death ligand 1Flow cytometryLung cancer mouse modelAdenoviral Cre recombinaseAutochthonous lung tumorsImmunomodulatory monoclonal antibodiesTumor-infiltrating CD8PD-L1 expressionSingle-agent therapyTumor-bearing lungsDeath ligand 1Tumor-free miceLung cancer modelCombinatorial antitumor effectCancer mouse modelCell populations
2017
Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice
Gibb DR, Liu J, Natarajan P, Santhanakrishnan M, Madrid DJ, Eisenbarth SC, Zimring JC, Iwasaki A, Hendrickson JE. Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice. The Journal Of Immunology 2017, 199: 1041-1050. PMID: 28630094, PMCID: PMC5568771, DOI: 10.4049/jimmunol.1700401.Peer-Reviewed Original ResearchConceptsRBC alloimmunizationRed blood cell alloimmunizationCertain inflammatory disordersCompatible blood productsProduction of alloantibodiesHemolytic transfusion reactionsCytosolic pattern recognition receptorsType I IFNsTransgenic murine modelType I IFNPattern recognition receptorsTransfusion protocolAlloimmune responseRBC transfusionInflammatory disordersInflammatory conditionsTransfusion reactionsBlood productsInflammatory stimuliMurine modelI IFNsAlloimmunizationI IFNViral infectionRecognition receptors
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
2014
Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation
Khan S, Toyoda H, Linehan M, Iwasaki A, Nomoto A, Bernhardt G, Cello J, Wimmer E. Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation. Journal Of General Virology 2014, 95: 1668-1676. PMID: 24784416, PMCID: PMC4103066, DOI: 10.1099/vir.0.064535-0.Peer-Reviewed Original ResearchConceptsTg mouse modelPeyer's patchesOral routeGastrointestinal tractMouse modelTransgenic miceImmunocompetent transgenic mouseHuman PV receptorCD155 tg miceSurface of enterocytesTgPVR21 miceCD155 expressionParenteral inoculationTg miceIntracerebral inoculationOral infectionYoung miceGut infectionLymphatic tissueGerminal centersPV infectionPV replicationPV receptorSmall intestineHuman CD155
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
2012
Adaptor 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
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 responses
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 layerCellsAutophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells. Science 2007, 315: 1398-1401. PMID: 17272685, DOI: 10.1126/science.1136880.Peer-Reviewed Original ResearchConceptsPlasmacytoid dendritic cellsToll-like receptorsDendritic cellsInterferon-alpha secretionLive viral infectionPDC responsesViral infectionViral recognitionViral replicationPathogen signaturesTLR7VirusSuch virusesVirus detectionProcess of autophagyAutophagyRNA virusesCellsInfectionPresent evidenceSecretionReceptors
2003
CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells
Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, Kaminogawa S. CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells. The Journal Of Immunology 2003, 171: 3684-3690. PMID: 14500666, DOI: 10.4049/jimmunol.171.7.3684.Peer-Reviewed Original ResearchConceptsPP dendritic cellsNaive B cellsDendritic cellsIL-6B cellsIgA secretionDC subsetsIgA productionPeyer's patch dendritic cellsSecrete IL-6Exogenous IL-6Cell coculture systemDC populationsLymphoid organsCytokine secretionAb productionT cellsHigh levelsSpleenSecretionCoculture systemCellsIgAUnique roleDistinct capacitiesVaginal 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
Immunofluorescence Analysis of Poliovirus Receptor Expression in Peyer’s Patches of Humans, Primates, and CD155 Transgenic Mice: Implications for Poliovirus Infection
Iwasaki A, Welker R, Mueller S, Linehan M, Nomoto A, Wimmer E. Immunofluorescence Analysis of Poliovirus Receptor Expression in Peyer’s Patches of Humans, Primates, and CD155 Transgenic Mice: Implications for Poliovirus Infection. The Journal Of Infectious Diseases 2002, 186: 585-592. PMID: 12195344, DOI: 10.1086/342682.Peer-Reviewed Original ResearchConceptsFollicle-associated epitheliumPeyer's patchesCD155 expressionGerminal centersPoliovirus infectionGastrointestinal-associated lymphoid tissueIntestinal epitheliumPoliovirus receptor (PVR) expressionExpression of CD155Human poliovirus receptorCD155 tg miceCertain primate speciesTg miceLymphoid tissueOral infectionReceptor expressionMicrofold cellsTransgenic miceTunica muscularisCD155 transgenic micePoliovirus receptorRhesus macaquesInfectionM cellsEpithelium
2001
Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells
Iwasaki A, Kelsall B. Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells. The Journal Of Immunology 2001, 166: 4884-4890. PMID: 11290765, DOI: 10.4049/jimmunol.166.8.4884.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDB7-1 AntigenB7-2 AntigenCD8 AntigensCell LineageCell SeparationDendritic CellsEpithelial CellsEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IIImmunophenotypingInterferon-gammaInterleukin-10Interleukin-12Interleukin-4Lectins, C-TypeLymphocyte ActivationLymphocyte SubsetsMacrophage-1 AntigenMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMinor Histocompatibility AntigensMyeloid CellsPeyer's PatchesReceptors, Cell SurfaceSpleenT-LymphocytesUp-RegulationConceptsMyeloid dendritic cellsDendritic cellsCD40 ligand trimerDC subsetsIL-12p70IL-10T cellsPeyer's patch dendritic cellsIFN-gamma productionSoluble CD40 ligand trimerMucosal lymphoid tissuesNaive T cellsFollicle-associated epitheliumMurine Peyer's patchesNonmucosal sitesDC subpopulationsSubepithelial domeIL-4Lymphoid tissuePeyer's patchesMicrobial stimuliInterfollicular regionsIFN-gammaSurface phenotypeMucosal tissues
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 decreaseMiceImmunityPostvaccination
1999
Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells
Iwasaki A, Kelsall B. Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells. Journal Of Experimental Medicine 1999, 190: 229-240. PMID: 10432286, PMCID: PMC2195574, DOI: 10.1084/jem.190.2.229.Peer-Reviewed Original ResearchConceptsPP dendritic cellsDendritic cellsNaive T cellsPeyer's patchesT cellsIL-10DC populationsImmune responseT cell receptor transgenic miceAllogeneic T cell proliferationT helper type 2 cellsT helper cell responsesMajor histocompatibility complex (MHC) class II moleculesIsolated Peyer's patchesSurface phenotypic analysisVivo dendritic cellsHelper cell responsesIL-10 secretionPrime T cellsDistinct immune responsesReceptor transgenic miceAntigen-presenting cellsIFN-gamma productionProduction of interleukinT cell proliferation