2022
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
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 cytokinesLes vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales
Thomas JL, Song E, Boisserand L, Iwasaki A. Les vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales. Médecine/sciences 2020, 36: 709-713. PMID: 32821046, PMCID: PMC8158397, DOI: 10.1051/medsci/2020141.Peer-Reviewed Original Research
2016
AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
Schmid ET, Pang IK, Silva E, Bosurgi L, Miner JJ, Diamond MS, Iwasaki A, Rothlin CV. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. ELife 2016, 5: e12414. PMID: 27350258, PMCID: PMC4924996, DOI: 10.7554/elife.12414.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonDendritic cellsIL-1βAntiviral T cell immunityAntiviral adaptive immunityPotent immunosuppressive functionT cell immunityT cell primingInhibition of AXLType I IFN receptorAxl receptor tyrosine kinaseReceptor tyrosine kinase AXLControl of infectionType I interferonI IFN receptorTyrosine kinase AXLDC maturationCell immunityWest Nile virusCell primingImmunosuppressive functionImmunosuppressive effectsAdaptive immunity
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 findingsCellsInfectionFindingsCandida 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
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 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
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 ResearchMeSH KeywordsAnimalsCell MovementHumansImmunologic MemoryInflammationLymphocyte ActivationPhenotypeT-Lymphocyte SubsetsVaccinesVirus DiseasesVirusesConceptsMemory 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 memoryIL-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
2011
CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input
Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A. CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8749-8754. PMID: 21555577, PMCID: PMC3102372, DOI: 10.1073/pnas.1100567108.Peer-Reviewed Original ResearchConceptsT cellsDendritic cellsCytotoxic T-lymphocyte primingT lymphocyte responsesAntigen-specific CTLsT lymphocyte primingSecondary lymphoid organsT cell helpCD40-dependent mannerNaïve B cellsCognate CTLsAcute infectionLymph nodesLymphocyte primingLymphocyte responsesLymphocyte recruitmentCTL expansionLymphoid organsImmune responseNaïve precursorsB cellsImmune systemReactive LNsIntracellular pathogensInfection
2010
In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells
Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, Mizushima N, Grinstein S, Iwasaki A. In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells. Immunity 2010, 32: 227-239. PMID: 20171125, PMCID: PMC2996467, DOI: 10.1016/j.immuni.2009.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutophagy-Related Protein 5Cells, CulturedDendritic CellsFemaleHerpes SimplexHerpesvirus 2, HumanHistocompatibility Antigens Class IILymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsRadiation ChimeraRNA, Small InterferingConceptsMHC-II presentationMHC class IIDendritic cellsAntigen presentationClass IIHerpes simplex virus infectionToll-like receptor stimuliT cell primingSimplex virus infectionCell primingAbsence of ATG5Microbial antigensVirus infectionMHC ICytosolic antigensConditional deletionAntigenReceptor stimuliAutophagic machineryKey autophagy genesRapid diseasePresentationATG5Lysosome fusionAutophagy genes
2009
Local advantage: skin DCs prime; skin memory T cells protect
Iwasaki A. Local advantage: skin DCs prime; skin memory T cells protect. Nature Immunology 2009, 10: 451-453. PMID: 19381136, PMCID: PMC3662044, DOI: 10.1038/ni0509-451.Peer-Reviewed Original ResearchMeSH KeywordsDendritic CellsHumansImmunologic MemoryLymphocyte ActivationSkinSkin Diseases, InfectiousT-Lymphocytes, Cytotoxic
2007
Innate control of adaptive immunity: Dendritic cells and beyond
Lee HK, Iwasaki A. Innate control of adaptive immunity: Dendritic cells and beyond. Seminars In Immunology 2007, 19: 48-55. PMID: 17276695, DOI: 10.1016/j.smim.2006.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritic CellsHumansImmunity, InnateLymphocyte ActivationT-Lymphocytes, RegulatoryToll-Like ReceptorsConceptsDendritic cellsAdaptive immune responsesImmune responseInnate immune recognitionKey cell typesCell typesEffector cellsNaïve lymphocytesAdaptive immunityInnate controlImmune recognitionAnatomical locationImmediate defensePathogen triggersCellsRecent understandingLymphocytesInfectionImmunityResponseDivision of Labor by Dendritic Cells
Iwasaki A. Division of Labor by Dendritic Cells. Cell 2007, 128: 435-436. PMID: 17289563, DOI: 10.1016/j.cell.2007.01.024.Peer-Reviewed Original Research
2004
Toll-like receptor control of the adaptive immune responses
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nature Immunology 2004, 5: 987-995. PMID: 15454922, DOI: 10.1038/ni1112.Peer-Reviewed Original ResearchConceptsToll-like receptorsAdaptive immune responsesImmune responseMechanisms of TLRToll-like receptor controlHost defense responsesDendritic cell functionDendritic cell populationsMicrobial infectionsInnate immune systemDistinct anatomical locationsInflammatory reactionAdaptive immunityImmune systemAnatomical locationReceptor controlCell functionCell populationsMultiple mechanismsInfectionRecent studiesResponseInitiationSystemic defenseImportant cluesMAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection
Soderberg KA, Linehan MM, Ruddle NH, Iwasaki A. MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection. The Journal Of Immunology 2004, 173: 1908-1913. PMID: 15265924, DOI: 10.4049/jimmunol.173.3.1908.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralCD4-Positive T-LymphocytesCell Adhesion MoleculesDendritic CellsFemaleHerpes GenitalisHerpesvirus 2, HumanImmunoglobulin GImmunoglobulinsLymph NodesLymphocyte ActivationLymphotoxin-alphaLymphotoxin-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMucoproteinsSacrococcygeal RegionSplenectomyT-Cell Antigen Receptor SpecificityTh1 CellsVaginitisConceptsBeta-deficient miceSacral lymph nodesLymph nodesMesenteric lymph nodesWild-type miceGenital mucosaHerpes simplex virus 2 infectionIntravaginal HSV-2 infectionLT alpha-deficient miceMucosal addressin cell adhesion molecule-1Simplex virus 2 infectionCell adhesion molecule-1Mucosal lymph nodesAlpha-deficient miceCervical lymph nodesHSV-2 infectionVirus 2 infectionHSV type 2Potent immune responsesAdhesion molecule-1Intravaginal infectionTh1 responseDendritic cellsIgG responsesIliac artery
2003
Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
Zhao X, Deak E, Soderberg K, Linehan M, Spezzano D, Zhu J, Knipe DM, Iwasaki A. Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2. Journal Of Experimental Medicine 2003, 197: 153-162. PMID: 12538655, PMCID: PMC2193810, DOI: 10.1084/jem.20021109.Peer-Reviewed Original ResearchConceptsSubmucosal dendritic cellsDendritic cellsLymph nodesHSV-2T cellsIFNgamma secretionLangerhans cellsVaginal mucosaHerpes simplex virus type 2 infectionSimplex virus type 2 infectionViral peptidesProtective Th1 immune responseVirus type 2 infectionHerpes simplex virus 2Genital mucosal surfacesHSV-2 infectionProtective Th1 responseTh1 immune responseMHC class II moleculesProtective Th1 immunityAntigen-presenting cellsType 2 infectionSimplex virus 2Class II moleculesDC populations
2002
The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo
Park MK, Amichay D, Love P, Wick E, Liao F, Grinberg A, Rabin RL, Zhang HH, Gebeyehu S, Wright TM, Iwasaki A, Weng Y, DeMartino JA, Elkins KL, Farber JM. The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo. The Journal Of Immunology 2002, 169: 1433-1443. PMID: 12133969, DOI: 10.4049/jimmunol.169.3.1433.Peer-Reviewed Original ResearchConceptsT cellsActivated B cellsB cellsDendritic cellsIFN-gammaIntracellular bacterium Francisella tularensis live vaccine strainChemotactic factorsCell activationFrancisella tularensis live vaccine strainRole of MIGT cell infiltrationTularensis live vaccine strainOptimal humoral responsesLive vaccine strainT cell activationB cell activationHuman T cellsReceptor CXCR3Humoral responseCell infiltrationLymphoid organsTarget lymphocytesCXC chemokinesInflammatory reactionPeripheral tissues
2001
Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells
Iwasaki A, Kelsall B. Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells. The Journal Of Immunology 2001, 166: 4884-4890. PMID: 11290765, DOI: 10.4049/jimmunol.166.8.4884.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDB7-1 AntigenB7-2 AntigenCD8 AntigensCell LineageCell SeparationDendritic CellsEpithelial CellsEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IIImmunophenotypingInterferon-gammaInterleukin-10Interleukin-12Interleukin-4Lectins, C-TypeLymphocyte ActivationLymphocyte SubsetsMacrophage-1 AntigenMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMinor Histocompatibility AntigensMyeloid CellsPeyer's PatchesReceptors, Cell SurfaceSpleenT-LymphocytesUp-RegulationConceptsMyeloid dendritic cellsDendritic cellsCD40 ligand trimerDC subsetsIL-12p70IL-10T cellsPeyer's patch dendritic cellsIFN-gamma productionSoluble CD40 ligand trimerMucosal lymphoid tissuesNaive T cellsFollicle-associated epitheliumMurine Peyer's patchesNonmucosal sitesDC subpopulationsSubepithelial domeIL-4Lymphoid tissuePeyer's patchesMicrobial stimuliInterfollicular regionsIFN-gammaSurface phenotypeMucosal tissues
2000
Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells
Gurunathan S, Stobie L, Prussin C, Sacks D, Glaichenhaus N, Iwasaki A, Fowell D, Locksley R, Chang J, Wu C, Seder R. Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells. The Journal Of Immunology 2000, 165: 915-924. PMID: 10878366, DOI: 10.4049/jimmunol.165.2.915.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ProtozoanCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8 AntigensCD8-Positive T-LymphocytesCell DivisionCells, CulturedDNA, ProtozoanGenes, T-Cell Receptor betaImmune SeraImmunity, CellularInjections, SubcutaneousInterferon-gammaInterleukin-12Leishmania majorLeishmaniasis, CutaneousLymph NodesLymphocyte ActivationMiceMice, Inbred BALB CMice, TransgenicProtein Kinase CProtozoan ProteinsReceptors, InterleukinReceptors, Interleukin-12Th1 CellsVaccines, DNAConceptsIFN-gamma-producing T cellsDepletion of CD8DNA-vaccinated miceT cellsDNA vaccinationProtective immunityImmunoregulatory roleWk postvaccinationLong-term protective immunityLACK-specific CD4Time of vaccinationPotential immunoregulatory roleNovel immunoregulatory roleTh1 immunityIL-12Th1 cellsInfectious challengeCD8VaccinationInfectionLeishmania majorStriking decreaseMiceImmunityPostvaccination