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
2018
Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
Lucas CGO, Kitoko JZ, Ferreira FM, Suzart VG, Papa MP, Coelho SVA, Cavazzoni CB, Paula-Neto HA, Olsen PC, Iwasaki A, Pereira RM, Pimentel-Coelho PM, Vale AM, de Arruda LB, Bozza MT. Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection. Nature Communications 2018, 9: 3136. PMID: 30087337, PMCID: PMC6081430, DOI: 10.1038/s41467-018-05519-4.Peer-Reviewed Original ResearchConceptsT cellsZika virusMurine adoptive transfer modelParticipation of CD4Adoptive transfer modelT cell responsesImportance of CD4Protective adaptive immunityRapid disease onsetZika virus infectionFuture vaccine designAntibody-mediated resistanceCytotoxic CD8Viral loadZIKV infectionAntibody responsePrimary infectionRecipient miceDisease onsetVirus infectionProtective effectAdaptive immunityIFNγ signalingCD4B lymphocytes
2017
Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense
Sasai M, Sakaguchi N, Ma JS, Nakamura S, Kawabata T, Bando H, Lee Y, Saitoh T, Akira S, Iwasaki A, Standley DM, Yoshimori T, Yamamoto M. Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense. Nature Immunology 2017, 18: 899-910. PMID: 28604719, DOI: 10.1038/ni.3767.Peer-Reviewed Original ResearchADP-Ribosylation Factor 1AnimalsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 8 FamilyCarrier ProteinsComputer SimulationCRISPR-Cas SystemsCytoskeletal ProteinsEnzyme-Linked Immunosorbent AssayFlow CytometryFluorescent Antibody TechniqueGene EditingGTP PhosphohydrolasesImmunoblottingImmunoprecipitationInterferon-gammaIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMicrotubule-Associated ProteinsToxoplasmaToxoplasmosis
2016
Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature 2016, 533: 552-556. PMID: 27225131, PMCID: PMC4883597, DOI: 10.1038/nature17979.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralBiological TransportBlood-Brain BarrierB-LymphocytesCapillary PermeabilityCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGanglia, SpinalHerpes GenitalisHerpesvirus 2, HumanHistocompatibility Antigens Class IImmunologic MemoryIntegrin alpha4Interferon-gammaMiceNerve TissueNervous SystemNeuronsNoseReceptors, FcSpinal CordVesiculovirus
2014
Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function
Guo YE, Riley KJ, Iwasaki A, Steitz JA. Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function. Molecular Cell 2014, 54: 67-79. PMID: 24725595, PMCID: PMC4039351, DOI: 10.1016/j.molcel.2014.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteBase SequenceCallithrixEnzyme ActivationGene Expression RegulationGPI-Linked ProteinsGRB2 Adaptor ProteinHEK293 CellsHerpesvirus 2, SaimiriineHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansImmunoprecipitationInterferon-gammaJurkat CellsLectins, C-TypeLymphocyte ActivationMicroRNAsMitogen-Activated Protein KinasesMolecular Sequence DataReceptors, Antigen, T-CellRNA StabilityRNA, UntranslatedRNA, ViralSemaphorinsSequence Analysis, RNASignal TransductionT-LymphocytesTime FactorsTransfectionConceptsMitogen-activated protein kinaseMiR-27Protein coding genesHerpesvirus saimiriHigh-throughput sequencingTCR-induced activationCell functionHSUR 1Γ-herpesvirusesNoncoding RNAsProtein kinaseEctopic expressionOncogenic γ-herpesvirusesTarget genesInduction of CD69MicroRNA-27Key modulatorRNACommon targetAlHV-1GenesCell receptorDiverse strategiesHost T-cell functionCellsEpigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth
Ding S, Khoury-Hanold W, Iwasaki A, Robek MD. Epigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth. PLOS Biology 2014, 12: e1001758. PMID: 24409098, PMCID: PMC3883642, DOI: 10.1371/journal.pbio.1001758.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCpG IslandsCricetinaeCytomegalovirusDNA MethylationEpigenesis, GeneticHepatocytesHerpesvirus 1, HumanHistone Deacetylase InhibitorsHistone DeacetylasesHost-Pathogen InteractionsHumansInterferon-gammaMiceNIH 3T3 CellsOrgan SpecificityPromoter Regions, GeneticReceptors, CytokineReceptors, InterferonRNA, Small InterferingSignal TransductionVesiculovirusConceptsHDAC inhibitorsPro-apoptotic activityRepression machineryExpression programsTranscriptional silencingEpigenetic reprogrammingEpigenetic rewiringUbiquitous expressionMolecular mechanismsCell typesSpecific mannerSuppress tumor growthReceptor subunitsPotential antitumor strategyNonresponsive cellsIFN responseAntiviral immunityViral pathogensExpressionReceptor expressionType III interferonsAntitumor strategyΒ receptorTumor growthEpithelial origin
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
2009
CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help
Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature 2009, 462: 510-513. PMID: 19898495, PMCID: PMC2789415, DOI: 10.1038/nature08511.Peer-Reviewed Original ResearchConceptsT cell helpT cellsRecruitment of CD8Activity of CD4T lymphocyte responsesT helper cellsSecretion of interferonLymphocyte mobilizationCD4 helpCTL responsesCytotoxic CD8Lymphocyte responsesMucosal sitesChemokine secretionHelper cellsVirus-infected tissuesViral infectionCD4CD8Intracellular pathogensSecretionUnrecognized aspectsCellsInterferonInfectionCholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function
la Sala A, He J, Laricchia-Robbio L, Gorini S, Iwasaki A, Braun M, Yap GS, Sher A, Ozato K, Kelsall B. Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function. Journal Of Experimental Medicine 2009, 206: 1227-1235. PMID: 19487420, PMCID: PMC2715075, DOI: 10.1084/jem.20080912.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8 AntigensCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCholera ToxinCyclic AMPDendritic CellsFemaleGTP-Binding Protein alpha Subunits, GsHumansInterferon Regulatory Factor-1Interferon Regulatory FactorsInterferon-gammaInterleukin-12Interleukin-12 Subunit p40MiceMice, Inbred BALB CSpleenToxoplasmosisConceptsIL-12 productionDendritic cellsPlasmacytoid DCsCholera toxinSerum IL-12 levelsIL-12 levelsPlasmacytoid dendritic cellsConventional dendritic cellsIL-12p40 promoterDendritic cell differentiationConventional DCsP40 gene expressionBone marrow cellsInterferon regulatory factor 8Regulatory factor 8Th1 responseDC differentiationIL-12p35Lymphoid organsToxoplasma gondiiMarrow cellsDibutyryl cAMPIRF8Factor 8Common mechanism[Mucosal immune defense against sexually transmitted diseases].
Iijima N, Iwasaki A. [Mucosal immune defense against sexually transmitted diseases]. Clinical Journal Of Japan 2009, 67: 2-4. PMID: 19177745.Peer-Reviewed Original Research
2008
Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus
Iijima N, Linehan MM, Zamora M, Butkus D, Dunn R, Kehry MR, Laufer TM, Iwasaki A. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. Journal Of Experimental Medicine 2008, 205: 3041-3052. PMID: 19047439, PMCID: PMC2605233, DOI: 10.1084/jem.20082039.Peer-Reviewed Original ResearchConceptsMemory Th1 cellsDendritic cellsTh1 cellsB cellsIFN-gammaHerpes simplex virus 2 infectionAntiviral protectionSimplex virus 2 infectionMemory CD4 T cellsFurther viral replicationTh1 memory responseHSV-2 infectionCD4 T cellsLocal dendritic cellsVirus 2 infectionAntigen-presenting cellsCytotoxic T lymphocytesMHC class IISite of infectionHerpes simplex virusTh1 responseImmunized miceRecall responsesViral antigensMHC class
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
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 decreaseMiceImmunityPostvaccinationPrimary 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