2021
Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reduction
2020
Sex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesLongitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
2019
Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiet, KetogenicInfluenza A virusMiceMice, Inbred C57BLMice, KnockoutOrthomyxoviridae InfectionsT-LymphocytesConceptsΓδ T cellsKetogenic dietIAV infectionT cellsGlobal health care concernHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionHealth care concernHigh-carbohydrate dietInfluenza diseaseKD feedingVirus infectionNew therapiesAntiviral resistanceHepatic ketogenesisCare concernsCell responsesInfectionBarrier functionDietMetabolic adaptation
2017
Immune Regulation of Antibody Access to Neuronal Tissues
Iwasaki A. Immune Regulation of Antibody Access to Neuronal Tissues. Trends In Molecular Medicine 2017, 23: 227-245. PMID: 28185790, PMCID: PMC5626569, DOI: 10.1016/j.molmed.2017.01.004.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBlood-nerve barrierAdaptive immune systemImmune systemAntibody accessInnate immune controlUse of vaccinesImmune controlNeurotropic virusesCancer immunotherapyImmune regulationImmune surveillanceT cellsTAM receptorsNeurodegenerative conditionsAlzheimer's diseaseNeuronal tissueNeural tissueDiseaseTissueNovel insightsSuch novel insightsImmunotherapyCD4Cells
2016
AXL 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
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 TransductionTime FactorsT-LymphocytesTransfectionConceptsMitogen-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 functionCells
2012
A vaccine strategy that protects against genital herpes by establishing local memory T cells
Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491: 463-467. PMID: 23075848, PMCID: PMC3499630, DOI: 10.1038/nature11522.Peer-Reviewed Original ResearchPhagosome as the Organelle Linking Innate and Adaptive Immunity
Kagan JC, Iwasaki A. Phagosome as the Organelle Linking Innate and Adaptive Immunity. Traffic 2012, 13: 1053-1061. PMID: 22577865, PMCID: PMC3658133, DOI: 10.1111/j.1600-0854.2012.01377.x.Peer-Reviewed Original ResearchConceptsProcess of phagocytosisPhagosome traffickingAdaptive immunityAntimicrobial defense mechanismsDefinable unitSubcellular levelT cell-mediated immunityAdaptive immune systemDefense mechanismsToll-like receptorsPhagosomesPhagocytosisImmune systemImmunityMicrobesTraffickingAutophagyPathwayReceptorsInnate
2009
Differential 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[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
2005
Intestinal epithelial barrier and mucosal immunity
Sato A, Iwasaki A. Intestinal epithelial barrier and mucosal immunity. Cellular And Molecular Life Sciences 2005, 62: 1333. PMID: 15971108, DOI: 10.1007/s00018-005-5037-z.Peer-Reviewed Original ResearchConceptsDendritic cellsMucosal immunityPeyer's patchesMajor inductive siteMucosal dendritic cellsPP dendritic cellsResident dendritic cellsMucosal immune systemIntestinal epithelial barrierFood antigensInductive sitesGastrointestinal mucosaT cellsImmune inductionImmune responseRecent studiesEpithelial barrierImmune systemCommensal microbesSmall intestineA responsesInfectious pathogensImmunityAntigenInduction
2004
Involvement of Dendritic Cell Subsets in the Induction of Oral Tolerance and Immunity
FLEETON M, CONTRACTOR N, LEON F, HE J, WETZEL D, DERMODY T, IWASAKI A, KELSALL B. Involvement of Dendritic Cell Subsets in the Induction of Oral Tolerance and Immunity. Annals Of The New York Academy Of Sciences 2004, 1029: 60-65. PMID: 15681744, DOI: 10.1196/annals.1309.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritic CellsImmune ToleranceImmunity, MucosalMicePeyer's PatchesReoviridae InfectionsT-LymphocytesConceptsSubepithelial dome regionDendritic cellsApoptotic epithelial cellsDC maturationEpithelial cellsOral administrationT cellsImmune responsePP follicle-associated epitheliumSystemic antiviral immune responsesDendritic cell subsetsPlasmacytoid dendritic cellsCross-present antigensRegulatory T cellsInduction of immunityB cell responsesAntiviral immune responseActive viral infectionFollicle-associated epitheliumMurine Peyer's patchesDC infectionDC subsetsOral antigenDC populationsOral toleranceToll-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
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
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
1999
I. Mucosal dendritic cells: their specialized role in initiating T cell responses*
Iwasaki A, Kelsall B. I. Mucosal dendritic cells: their specialized role in initiating T cell responses*. American Journal Of Physiology 1999, 276: g1074-g1078. PMID: 10329996, DOI: 10.1152/ajpgi.1999.276.5.g1074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritic CellsHumansInflammationIntestinal MucosaMucous MembranePeyer's PatchesPhenotypeT-LymphocytesConceptsT cell responsesMucosal dendritic cellsDendritic cellsCell responsesCompetent antigen-presenting cellsPrimary T cell responsesTissue-resident dendritic cellsResident dendritic cellsAntigen-presenting cellsDC populationsLymphoid tissueRecent studiesCellsFunctional studiesResponseMucosaIsolation procedureSpecialized role