2020
m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liver
2017
B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice
Gibb DR, Liu J, Santhanakrishnan M, Natarajan P, Madrid DJ, Patel S, Eisenbarth SC, Tormey CA, Stowell SR, Iwasaki A, Hendrickson JE. B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice. Transfusion 2017, 57: 2595-2608. PMID: 28836263, PMCID: PMC5745367, DOI: 10.1111/trf.14288.Peer-Reviewed Original ResearchConceptsBone marrow chimeric miceHuman KEL glycoproteinType 1 interferonB cellsMean fluorescence intensityChimeric miceRed blood cell antigensBlood cell antigensGerminal center B cellsWT B cellsRBC alloimmunizationIgG alloantibodiesAlloimmune responseB cell differentiationRed blood cellsTransfusion protocolControl miceInflammatory stateWT miceAutoimmune pathologyIgG productionIFNAR1 expressionPlasma cellsAntiviral immunityInflammatory stimuli
2015
Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation
Kashem SW, Igyártó B, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity 2015, 42: 356-366. PMID: 25680275, PMCID: PMC4343045, DOI: 10.1016/j.immuni.2015.01.008.Peer-Reviewed Original ResearchConceptsT helper cell responsesHelper cell responsesCell responsesInterleukin-6Systemic infectionDectin-1 ligationTh1 cell responsesTh cell responsesT helper 17 (Th17) cell differentiationT helper cell differentiationTissue-specific protectionSkin infection modelMurine skin infection modelC. albicansHelper cell differentiationMucocutaneous immunityCutaneous infectionsVaccine strategiesLangerhans cellsSystemic immunityT cellsCell differentiationInfection modelInfectionImmunity
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 subsetCD301bHigh-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells
Iijima N, Goodwin EC, DiMaio D, Iwasaki A. High-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells. Virology 2013, 444: 257-262. PMID: 23871219, PMCID: PMC3755085, DOI: 10.1016/j.virol.2013.06.020.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCells, CulturedCoculture TechniquesFemaleHumansImmune EvasionLangerhans CellsMonocytesOncogene Proteins, ViralPapillomaviridaeConceptsHigh-risk human papillomavirusLangerhans cellsHigh-risk HPVCompetent antigen presenting cellsHPV-positive cancer cellsKey antigen-presenting cellsHPV-positive cervical cancer cellsCancer cellsHuman peripheral blood monocytesAntigen-presenting cellsAntigen presenting cellsImmune evasion strategiesPeripheral blood monocytesVariety of malignanciesCervical cancer cellsContact-dependent mannerDifferentiation of monocytesHuman papillomavirusPresenting cellsImmune surveillanceSquamous epitheliumBlood monocytesMucosal epitheliumHPV E6HPV16 E6IL-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 7
2012
Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells
Mantegazza AR, Guttentag SH, El-Benna J, Sasai M, Iwasaki A, Shen H, Laufer TM, Marks MS. Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells. Immunity 2012, 36: 782-794. PMID: 22560444, PMCID: PMC3361531, DOI: 10.1016/j.immuni.2012.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3AnimalsAntigen PresentationAntigensCD4-Positive T-LymphocytesCell DifferentiationCell MembraneCells, CulturedDendritic CellsEndocytosisHistocompatibility Antigens Class IILigandsListeria monocytogenesListeriosisMiceMice, Inbred C57BLMice, TransgenicMyeloid Differentiation Factor 88OvalbuminPeptidesPhagocytosisPhagosomesSignal TransductionTh1 CellsToll-Like ReceptorsConceptsToll-like receptor signalingDendritic cellsAntigen presentationAdaptor protein 3Protein 3Receptor signalingMHC-II presentationEffector cell functionListeria monocytogenes infectionTLR ligandsMonocytogenes infectionTLR4 recruitmentT cellsCell activationIntracellular storesPhagolysosome maturationCell functionPearl miceReceptor-mediated endocytosisAntigenPresentationMolecular mechanismsPhagosomesCell surfaceSignaling
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
Cholera 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
2004
Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
Sato A, Iwasaki A. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 16274-16279. PMID: 15534227, PMCID: PMC528964, DOI: 10.1073/pnas.0406268101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationCaspase 1Cell DifferentiationCell MovementDendritic CellsFemaleHerpesvirus 2, HumanImmunity, InnateInterleukin-12Membrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicReceptors, InterferonSignal TransductionStromal CellsTh1 CellsToll-Like ReceptorsConceptsToll-like receptorsT cell responsesPattern recognition receptorsViral infectionContribution of TLRsRecognition receptorsCell responsesEffector T cell responsesHerpes simplex virus type 2Simplex virus type 2Antiviral adaptive immunityDendritic cell compartmentEffector T cellsDendritic cell maturationMost viral infectionsVirus type 2Infected epithelial cellsMucosal infectionsT cellsAdaptive immunityAntiviral immunityInfectious agentsType 2Immune recognitionStromal cells
2000
Primary 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
1999
Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells
Iwasaki A, Kelsall B. Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells. Journal Of Experimental Medicine 1999, 190: 229-240. PMID: 10432286, PMCID: PMC2195574, DOI: 10.1084/jem.190.2.229.Peer-Reviewed Original ResearchConceptsPP dendritic cellsDendritic cellsNaive T cellsPeyer's patchesT cellsIL-10DC populationsImmune responseT cell receptor transgenic miceAllogeneic T cell proliferationT helper type 2 cellsT helper cell responsesMajor histocompatibility complex (MHC) class II moleculesIsolated Peyer's patchesSurface phenotypic analysisVivo dendritic cellsHelper cell responsesIL-10 secretionPrime T cellsDistinct immune responsesReceptor transgenic miceAntigen-presenting cellsIFN-gamma productionProduction of interleukinT cell proliferation