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 ResearchMeSH KeywordsCytidine DeaminaseCytokinesGene Expression RegulationHumansInterferon-alphaResponse ElementsUbiquitinsConceptsGene 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 IFNTranscriptionSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2020
Commensal Microbiota Modulation of Natural Resistance to Virus Infection
Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal Microbiota Modulation of Natural Resistance to Virus Infection. Cell 2020, 183: 1312-1324.e10. PMID: 33212011, PMCID: PMC7799371, DOI: 10.1016/j.cell.2020.10.047.Peer-Reviewed Original ResearchConceptsMicrobial moleculesVesicular stomatitis virusCommensal microbesSpecific commensal microbesInduction of IFNVirus infectionNatural resistanceOuter membraneGut commensal microbesIFN-β expressionImmune system regulationHuman diseasesPhysiological importanceInduces expressionSource of IFNMicrobesHomeostatic conditionsStomatitis virusIFN-IsMicrobiota modulationAntiviral immunityCrucial mediatorIFNPolysaccharide AAntiviral activity
2019
The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV
Treger RS, Pope SD, Kong Y, Tokuyama M, Taura M, Iwasaki A. The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV. Immunity 2019, 50: 334-347.e9. PMID: 30709743, PMCID: PMC6382577, DOI: 10.1016/j.immuni.2018.12.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEndogenous RetrovirusesGene Expression RegulationGenetic Predisposition to DiseaseGlycoproteinsHEK293 CellsHumansLupus Erythematosus, SystemicLupus NephritisMiceMice, 129 StrainMice, Inbred C57BLMice, Inbred NZBMice, KnockoutMolecular ChaperonesNuclear ProteinsRepressor Proteins
2018
Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner
Gopinath S, Kim MV, Rakib T, Wong PW, van Zandt M, Barry NA, Kaisho T, Goodman AL, Iwasaki A. Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner. Nature Microbiology 2018, 3: 611-621. PMID: 29632368, PMCID: PMC5918160, DOI: 10.1038/s41564-018-0138-2.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, TopicalAminoglycosidesAnimalsAnti-Bacterial AgentsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGerm-Free LifeHumansInfluenza A virusMiceMicrobiotaOligonucleotide Array Sequence AnalysisSimplexvirusToll-Like Receptor 3Transcription FactorsVirus DiseasesVirus ReplicationZika VirusConceptsToll-like receptor 3Aminoglycoside treatmentInterferon-stimulated genesViral infectionReceptor 3ISG inductionAminoglycoside antibioticsMicrobiota-independent mannerGerm-free miceAdapter-inducing interferonInterferon regulatory factor 3Herpes simplex virusTopical mucosal applicationRegulatory factor 3Dendritic cellsAntibiotic useAntiviral effectAminoglycoside applicationHost resistanceSimplex virusAntiviral resistanceVaginal mucosaMarked upregulationMucosal applicationTopical applicationA minimal RNA ligand for potent RIG-I activation in living mice
Linehan MM, Dickey TH, Molinari ES, Fitzgerald ME, Potapova O, Iwasaki A, Pyle AM. A minimal RNA ligand for potent RIG-I activation in living mice. Science Advances 2018, 4: e1701854. PMID: 29492454, PMCID: PMC5821489, DOI: 10.1126/sciadv.1701854.Peer-Reviewed Original ResearchConceptsStem-loop RNAInterferon-stimulated genesImmune systemPotent synthetic activatorVertebrate immune systemType I interferonInnate immune systemRIG-I receptorRIG-I activationExpression networksRemodeling factorsPotent RIGRNA sequencingSpecific genesRNA ligandsI interferonAntiviral defenseInterferon responseRNA sensorsPolycytidylic acidSynthetic activatorsMiceInterferonGenesRNA
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 ResearchMitochondrial DNA stress primes the antiviral innate immune response
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520: 553-557. PMID: 25642965, PMCID: PMC4409480, DOI: 10.1038/nature14156.Peer-Reviewed Original Research
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
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
Autophagy and selective deployment of Atg proteins in antiviral defense
Yordy B, Tal MC, Hayashi K, Arojo O, Iwasaki A. Autophagy and selective deployment of Atg proteins in antiviral defense. International Immunology 2012, 25: 1-10. PMID: 23042773, PMCID: PMC3534236, DOI: 10.1093/intimm/dxs101.Peer-Reviewed Original ResearchConceptsAutophagy machineryAtg proteinsAntiviral defenseViral pathogen-associated molecular patternsPathogen-associated molecular patternsEukaryotic cellsCellular homeostasisCanonical autophagyViral replication sitesMajor histocompatibility complex presentationIntracellular transportAntiviral proteinCytosolic componentsRegulatory functionsEndolysosomal compartmentsReplication sitesAutophagyMachineryMolecular patternsDiverse repertoireIntracellular materialProteinToll-like receptorsViral antigen processingSelective targeting
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 migrationChemotaxisARHGEF5