2023
Developing synthetic tools to decipher the tumor–immune interactome
Weizman O, Luyten S, Lu P, Song E, Qin K, Mostaghimi D, Ring A, Iwasaki A. Developing synthetic tools to decipher the tumor–immune interactome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306632120. PMID: 37871202, PMCID: PMC10622925, DOI: 10.1073/pnas.2306632120.Peer-Reviewed Original ResearchConceptsImmune cellsImmune-based therapiesTumor-immune cell interactionsDifferent immunotherapiesRetroviral reportersSensitive tumorsImmune surveillanceTumor subtypesTumor microenvironmentSynthetic Notch receptorCell interactionsCell contactTissue functionTissue locationNotch receptorsVivoOptimal tissue functionCellsComprehensive landscapeImmunotherapyTherapyTumorsImmunogenicitySubtypesMature B cells and mesenchymal stem cells control emergency myelopoiesis
Lim V, Feng X, Miao R, Zehentmeier S, Ewing-Crystal N, Lee M, Tumanov A, Oh J, Iwasaki A, Wang A, Choi J, Pereira J. Mature B cells and mesenchymal stem cells control emergency myelopoiesis. Life Science Alliance 2023, 6: e202301924. PMID: 36717247, PMCID: PMC9889502, DOI: 10.26508/lsa.202301924.Peer-Reviewed Original ResearchConceptsMarrow mesenchymal stem cellsSystemic inflammationMature B cellsB cellsEmergency myelopoiesisMesenchymal stem cellsIL-1 receptorBone marrow mesenchymal stem cellsStem cellsMyeloid cell productionMonocyte numbersB lineage cellsCCL2 productionViral infectionLymphotoxin α1β2InflammationReduced survivalLymphopoietic activityMyelopoiesisLymphopoiesisImportant regulatorLTβRCell productionCellsGenetic blocking
2022
Multiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhate
2020
Experimental Evolution of Human Rhinovirus Strains Adapting to Mouse Cells
Wasik B, Wasik B, Foxman E, Iwasaki A, Turner P. Experimental Evolution of Human Rhinovirus Strains Adapting to Mouse Cells. Genetic And Evolutionary Computation 2020, 145-157. DOI: 10.1007/978-3-030-39831-6_12.Peer-Reviewed Original ResearchMouse cellsIdentical selection pressuresExperimental evolution studiesLaboratory tissue cultureCommon cold illnessesViral capsid geneMolecular divergenceExperimental evolutionReplication genesSelection pressureRelated populationsGenetic changesRNA virusesHuman rhinovirus strainsCapsid geneEvolution studiesRV-1BInnate immunityGenesTissue cultureDifferent strainsCellsLA-4 cellsHostMouse host
2019
RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling. Cell Reports 2019, 29: 3807-3815.e3. PMID: 31851914, DOI: 10.1016/j.celrep.2019.11.052.Peer-Reviewed Original ResearchConceptsRNA moleculesRIG-I activationBase pair sequenceHost RNA moleculesViral RNA moleculesRIG-I recognitionMolecular basisRNA variantsRNA targetsPair sequenceHuman cellsBase pairsImmune receptorsMechanisms of evasionTerminal base pairsLigand affinityWhole animalInterferon responseDeadly pathogenRNA therapeuticsMarburg virusCellsOverhangMoleculesSignalingApobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat
Taura M, Song E, Ho YC, Iwasaki A. Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 2282-2289. PMID: 30670656, PMCID: PMC6369738, DOI: 10.1073/pnas.1819386116.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCell LineCytidine DeaminaseEpigenesis, GeneticGene Expression Regulation, ViralGene SilencingHIV InfectionsHIV Long Terminal RepeatHIV-1HumansNF-kappa BProtein BindingProtein Interaction Domains and MotifsProteinsSequence DeletionSp1 Transcription FactorVirus ActivationVirus LatencyConceptsHIV-1 latencyHIV-1 reactivationCD4 T cellsT cellsHuman primary CD4 T cellsInfected CD4 T cellsHIV-1-infected cellsPrimary CD4 T cellsLong terminal repeat regionHIV-1Therapeutic strategiesLower reactivationProviral DNALatency maintenanceTarget cellsLatency stateCell linesLong terminal repeatTerminal repeat regionMolecular mechanismsReactivationCellsKnockdownA3AUnexpected role
2018
Publisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice
Jurado K, Yockey L, Wong P, Lee S, Huttner A, Iwasaki A. Publisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nature Microbiology 2018, 3: 255-255. DOI: 10.1038/s41564-017-0101-7.Peer-Reviewed Original Research
2017
RAB15 empowers dendritic cells to drive antiviral immunity
Wong P, Iwasaki A. RAB15 empowers dendritic cells to drive antiviral immunity. Science Immunology 2017, 2: eaan6448. PMID: 28783705, DOI: 10.1126/sciimmunol.aan6448.Peer-Reviewed Original ResearchImmune 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
2015
Tissue instruction for migration and retention of TRM cells
Iijima N, Iwasaki A. Tissue instruction for migration and retention of TRM cells. Trends In Immunology 2015, 36: 556-564. PMID: 26282885, PMCID: PMC4567393, DOI: 10.1016/j.it.2015.07.002.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsMemory lymphocyte clustersTRM cellsT cellsCD4 tissue-resident memory T cellsRobust local immune responseCD8 TRM cellsEffector T cellsLocal immune responseMemory T cellsNon-lymphoid tissuesLymphocyte clustersImmune responseInfectious agentsIncoming pathogensCell homingRecent findingsCellsInfectionFindingsCervicovaginal Microbiota: Simple Is Better
Gopinath S, Iwasaki A. Cervicovaginal Microbiota: Simple Is Better. Immunity 2015, 42: 790-791. PMID: 25992855, DOI: 10.1016/j.immuni.2015.05.006.Peer-Reviewed Original Research
2014
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux A, Jackson R, Harman CC, Li T, West AP, de Zoete MR, Wu Y, Yordy B, Lakhani SA, Kuan CY, Taniguchi T, Shadel GS, Chen ZJ, Iwasaki A, Flavell RA. Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA. Cell 2014, 159: 1563-1577. PMID: 25525875, PMCID: PMC4272443, DOI: 10.1016/j.cell.2014.11.037.Peer-Reviewed Original ResearchConceptsMitochondrial outer membrane permeabilizationCell deathOuter membrane permeabilizationType I interferonDNA-dependent activationCaspase-dependent mannerI interferonCGAS/STING pathwayMitochondrial DNAApoptotic caspasesMembrane permeabilizationActive caspasesProapoptotic caspasesMitochondriaCaspasesSTING pathwayIFN responseAntiviral immunityCentral roleDual controlPathwayProinflammatory typeInductionCellsActivationAlternative 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 functionCells
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
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 ResearchA Virological View of Innate Immune Recognition
Iwasaki A. A Virological View of Innate Immune Recognition. Annual Review Of Microbiology 2012, 66: 177-196. PMID: 22994491, PMCID: PMC3549330, DOI: 10.1146/annurev-micro-092611-150203.Peer-Reviewed Original ResearchSkin TRM mediates distributed border patrol
Shin H, Iwasaki A. Skin TRM mediates distributed border patrol. Cell Research 2012, 22: 1325-1327. PMID: 22565287, PMCID: PMC3434347, DOI: 10.1038/cr.2012.75.Peer-Reviewed Original Research
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 aspectsCellsInterferonInfection