2023
Mature 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
The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFNThe immunology and immunopathology of COVID-19
Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science 2022, 375: 1122-1127. PMID: 35271343, DOI: 10.1126/science.abm8108.Peer-Reviewed Original ResearchConceptsImmune responseAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionFatal COVID-19Coronavirus 2 infectionPost-acute sequelaeCOVID-19 pathophysiologyProlongation of symptomsLong COVID syndromeMajor unmet needCOVID-19SARS-CoV-2COVID syndromeDisease resolutionInflammatory processChronic illnessUnmet needDefinitive findingsImmunology researchCOVID-19 researchImmunopathologySequelaePathophysiologySyndrome
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
2019
Monocytes Inadequately Fill In for Meningeal Macrophages
Song E, Iwasaki A. Monocytes Inadequately Fill In for Meningeal Macrophages. Trends In Immunology 2019, 40: 463-465. PMID: 31072686, PMCID: PMC8135183, DOI: 10.1016/j.it.2019.04.004.Peer-Reviewed Original Research
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 stimuliType I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice
Gibb DR, Liu J, Natarajan P, Santhanakrishnan M, Madrid DJ, Eisenbarth SC, Zimring JC, Iwasaki A, Hendrickson JE. Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice. The Journal Of Immunology 2017, 199: 1041-1050. PMID: 28630094, PMCID: PMC5568771, DOI: 10.4049/jimmunol.1700401.Peer-Reviewed Original ResearchConceptsRBC alloimmunizationRed blood cell alloimmunizationCertain inflammatory disordersCompatible blood productsProduction of alloantibodiesHemolytic transfusion reactionsCytosolic pattern recognition receptorsType I IFNsTransgenic murine modelType I IFNPattern recognition receptorsTransfusion protocolAlloimmune responseRBC transfusionInflammatory disordersInflammatory conditionsTransfusion reactionsBlood productsInflammatory stimuliMurine modelI IFNsAlloimmunizationI IFNViral infectionRecognition receptorsβ-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2016
Autophagy Snuffs a Macrophage’s Inner Fire
Khoury-Hanold W, Iwasaki A. Autophagy Snuffs a Macrophage’s Inner Fire. Cell Host & Microbe 2016, 19: 9-11. PMID: 26764592, DOI: 10.1016/j.chom.2015.12.015.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 typeInductionCellsActivation
2013
Tissue‐resident memory T cells
Shin H, Iwasaki A. Tissue‐resident memory T cells. Immunological Reviews 2013, 255: 165-181. PMID: 23947354, PMCID: PMC3748618, DOI: 10.1111/imr.12087.Peer-Reviewed Original ResearchConceptsMemory T cellsHuman immunodeficiency virusHerpes simplex virusGenital tractT cellsPeripheral tissuesImmune systemTissue-resident memory T cellsMemory T cell migrationTissue-resident memory cellsT cell-based vaccinesMemory T cell populationsMemory T cell subsetsAntibody-based vaccinesT cell recruitmentT cell subsetsNew vaccination strategiesT cell populationsSecondary lymphoid organsNon-lymphoid tissuesPortal of entryT cell migrationAdaptive immune systemTRM cellsEffector memory
2012
Phagosome 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
Autophagic control of RLR signaling
Tal MC, Iwasaki A. Autophagic control of RLR signaling. Autophagy 2009, 5: 749-750. PMID: 19571662, PMCID: PMC3693554, DOI: 10.4161/auto.5.5.8789.Peer-Reviewed Original ResearchConceptsAbsence of autophagyReactive oxygen speciesPattern recognition receptorsRetinoic acid-inducible gene IAcid-inducible gene IATG5 knockout cellsImportance of autophagyInducible gene IPotent antiviral factorsLike receptor familyI interferonCytosolic signalingKnockout cellsCellular organellesAutophagy functionAutophagic controlGene IRNA virusesAutophagyReceptor familyType I interferonMitochondriaAntiviral factorsRecognition receptorsInfected cells
2005
Innate control of adaptive immunity via remodeling of lymph node feed arteriole
Soderberg KA, Payne GW, Sato A, Medzhitov R, Segal SS, Iwasaki A. Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 16315-16320. PMID: 16260739, PMCID: PMC1283434, DOI: 10.1073/pnas.0506190102.Peer-Reviewed Original ResearchConceptsLymph nodesNaïve lymphocytesAdaptive immunityInnate controlFeed arteriolesLocal lymph nodesSecondary lymphoid organsAntigen-specific stimulationInnate immune recognitionAntigen-specific lymphocytesPathogen-derived antigensAdaptive immune systemCognate lymphocytesLymphocyte recruitmentLymphoid organsForeign antigensImmune recognitionImmune systemCognate antigenLymphocytesVascular inputRare antigen-specific lymphocytesAntigenArteriolesImmunity
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