2023
Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
Barmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455-eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.Peer-Reviewed Original ResearchConceptsMRNA vaccinesSARS-CoV-2 mRNA vaccinesSARS-CoV-2 mRNA vaccinationC-reactive protein levelsB-type natriuretic peptidePeripheral blood mononuclear cellsCardiac tissue inflammationDeep immune profilingSerum soluble CD163Vaccine-associated myocarditisCohort of patientsBlood mononuclear cellsCytotoxic T cellsLate gadolinium enhancementHypersensitivity myocarditisElevated troponinMRNA vaccinationImaging abnormalitiesNK cellsImmune profilingKiller cellsMyeloid responseNatriuretic peptideHumoral mechanismsInflammatory cytokinesType 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
2022
APOBEC3A regulates transcription from interferon-stimulated response elements
Taura M, Frank JA, Takahashi T, Kong Y, Kudo E, Song E, Tokuyama M, Iwasaki A. APOBEC3A regulates transcription from interferon-stimulated response elements. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2011665119. PMID: 35549556, PMCID: PMC9171812, DOI: 10.1073/pnas.2011665119.Peer-Reviewed Original ResearchConceptsGene expressionResponse elementHost genomic lociInterferon-stimulated response elementRNA sequence analysisLong terminal repeatNegative feedback loopGenomic lociHuman genomeLethal mutationsProximal promoterHIV-1 transcriptionUnexpected roleIFN-I treatmentTerminal repeatDependent inductionViral genomeCytidine deaminaseISG15 inductionAntiviral responseA3AGenomeISG15 expressionType I IFNTranscription
2021
Challenges in interpreting cytokine data in COVID-19 affect patient care and management
Wang SY, Takahashi T, Pine AB, Damsky WE, Simonov M, Zhang Y, Kieras E, Price CC, King BA, Siegel MD, Desir GV, Lee AI, Iwasaki A, Chun HJ. Challenges in interpreting cytokine data in COVID-19 affect patient care and management. PLOS Biology 2021, 19: e3001373. PMID: 34358229, PMCID: PMC8372945, DOI: 10.1371/journal.pbio.3001373.Peer-Reviewed Original ResearchKynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesDiverse functional autoantibodies in patients with COVID-19
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.Peer-Reviewed Original ResearchConceptsPeripheral immune cell compositionSARS-CoV-2 infectionCOVID-19Effects of autoantibodiesTissue-associated antigensSpecific clinical characteristicsInnate immune activationImmune cell compositionCOVID-19 exhibitCOVID-19 manifestsAnalysis of autoantibodiesSARS-CoV-2Functional autoantibodiesMouse surrogateClinical characteristicsVirological controlClinical outcomesImmune activationMild diseaseAsymptomatic infectionAutoantibody reactivityDisease progressionHealthcare workersHigh prevalenceAutoantibodiesSex differences in immune responses
Takahashi T, Iwasaki A. Sex differences in immune responses. Science 2021, 371: 347-348. PMID: 33479140, DOI: 10.1126/science.abe7199.Peer-Reviewed Original ResearchConceptsImmune responseCOVID-19Sex differencesSevere COVID-19Risk of deathHigher mortality riskCOVID-19 mortalityPossible biological mechanismsCOVID-19 incidenceMale sexRisk factorsSevere diseaseHigh riskMortality riskMale sex biasOld maleSex-disaggregated dataBehavioral factorsBiological sex differencesDeathVulnerable groupsRiskBiological mechanismsMalesSex
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 cytokinesThe Role of Immune Factors in Shaping Fetal Neurodevelopment
Lu-Culligan A, Iwasaki A. The Role of Immune Factors in Shaping Fetal Neurodevelopment. Annual Review Of Cell And Developmental Biology 2020, 36: 1-28. PMID: 32722920, PMCID: PMC9034439, DOI: 10.1146/annurev-cellbio-021120-033518.Peer-Reviewed Original ResearchConceptsMaternal immune activationImmune factorsFetal neurodevelopmentMaternal immunityPoor neurological outcomeMaternal-fetal interfaceNeurological outcomeNormal pregnancyImmune activationImmune pathwaysPostnatal lifeNeurological disordersExperimental modelNeurodevelopmentNormal physiologyPregnancyVivo roleImmunityCritical participantsMaternal pathwayFactorsSequence of eventsPathogenesisUteroFetusesLongitudinal 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
2018
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development
Yockey LJ, Iwasaki A. Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development. Immunity 2018, 49: 397-412. PMID: 30231982, PMCID: PMC6152841, DOI: 10.1016/j.immuni.2018.07.017.Peer-Reviewed Original ResearchConceptsFetal developmentHealthy pregnancyImmune responseFetal immune responseRole of interferonPregnancy complicationsProinflammatory cytokinesSuccessful pregnancyCertain infectionsPregnant mothersImmune cellsInflammatory conditionsSevere diseasePregnancyFetal diseaseImmune systemCytokinesCongenital disorderPossible targetsInterferonFetusesInfectionDiseaseMothersComplications
2015
Control 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 Research
2013
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13910-13915. PMID: 23918369, PMCID: PMC3752242, DOI: 10.1073/pnas.1303275110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesFlow CytometryHistological TechniquesImmunity, InnateImmunohistochemistryInfluenza A virusMembrane GlycoproteinsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRespiratory Tract InfectionsSignal TransductionToll-Like Receptor 7Viral LoadVirus ReplicationConceptsToll-like receptor 7Innate immune responseRespiratory tractInfected wild-type miceHost innate immune responseAirways of miceViral target cellsWild-type miceAcid-inducible gene 1RIG-I pathwayPattern recognition receptorsHost innate defenseViral replication efficiencyInflammatory mediatorsBronchoalveolar lavageViral loadProinflammatory programProinflammatory responseReceptor 7IAV infectionInflammatory responseVirus infectionLow doseViral replicationVirus replication
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 protectionMonocytesInfectionBifurcation 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 traffickingInfluenza 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 Replication
2009
[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 ResearchInflammasomes in viral infection
Ichinohe T, Iwasaki A. Inflammasomes in viral infection. Uirusu 2009, 59: 13. PMID: 19927984, DOI: 10.2222/jsv.59.13.Peer-Reviewed Original ResearchConceptsNOD-like receptorsProinflammatory cytokine interleukin-1betaRole of inflammasomesInfluenza virus infectionCytokine interleukin-1betaInnate immune responseCaspase-1 activationIL-33IL-18NLRP3 inflammasomeVirus infectionImmune responseInterleukin-1betaAdaptive immunityInflammasome activationMicrobial motifsDamage-associated signalsViral infectionInflammasomeMultiprotein complexesAdaptor proteinInfectionCertain virusesCell deathIntracellular sensors
2008
Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node
Thompson JM, Nicholson MG, Whitmore AC, Zamora M, West A, Iwasaki A, Staats HF, Johnston RE. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node. The Journal Of Immunology 2008, 181: 574-585. PMID: 18566424, PMCID: PMC3603373, DOI: 10.4049/jimmunol.181.1.574.Peer-Reviewed Original ResearchConceptsDraining Lymph NodesVirus replicon particlesMucosal immune responsesMucosal lymphoid tissuesImmune inductionAg deliveryIgA AbsLymph nodesLymphoid tissueImmune responseMucosal surfacesMucosal addressin cell adhesion molecule-1Strong mucosal immune responsesEncephalitis virus replicon particlesCell adhesion molecule-1Multiple mucosal surfacesViral-based vaccinesAdhesion molecule-1Lymphoid structuresIL-6Immunological parametersImmunological componentsCC chemokinesIgA detectionReplicon particles
2006
Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells
Sato A, Linehan MM, Iwasaki A. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 17343-17348. PMID: 17085599, PMCID: PMC1859932, DOI: 10.1073/pnas.0605102103.Peer-Reviewed Original ResearchConceptsToll-like receptorsHerpes simplex virusMultiple Toll-like receptorsDendritic cellsSimplex virusBone marrow-derived dendritic cellsMarrow-derived dendritic cellsMultiple pathogen-associated molecular patternsPrimary clinical isolatesIL-12 secretionConventional dendritic cellsSame dendritic cellInnate immune systemPathogen-associated molecular patternsViral infection resultsProinflammatory cytokinesSurface TLR2IL-6Infection resultsTLR2TLR9Viral recognitionImmune systemClinical isolatesAdditional agonists