2023
Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity
Weizman O, Luyten S, Krykbaeva I, Song E, Mao T, Bosenberg M, Iwasaki A. Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity. The Journal Of Immunology 2023, 210: 1146-1155. PMID: 36881866, PMCID: PMC10067787, DOI: 10.4049/jimmunol.2200697.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesDendritic CellsImmunity, InnateKiller Cells, NaturalMiceSignal TransductionConceptsType 2 dendritic cellsMetastatic burdenImmune circuitsDendritic cellsConventional type 2 dendritic cellsSyngeneic murine melanomaNK cell compartmentImmune cell responsesColon cancer modelEarly metastatic seedingMetastatic controlTranscription factor IRF3DC populationsNK cellsProinflammatory cytokinesNucleic acid sensingPrimary tumorEffector responsesMetastatic spreadDisease outcomeIntracardiac injectionT cellsInitial immunityTissue-specific ablationCancer modelIL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii
Clark J, Weizman O, Aldridge D, Shallberg L, Eberhard J, Lanzar Z, Wasche D, Huck J, Zhou T, Ring A, Hunter C. IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii. Cell Reports 2023, 42: 112147. PMID: 36827187, PMCID: PMC10131179, DOI: 10.1016/j.celrep.2023.112147.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansImmunity, InnateInterleukin-12Interleukin-18Killer Cells, NaturalToxoplasmaToxoplasmosis, AnimalConceptsInnate lymphoid cellsIL-18IL-18BPNatural killerToxoplasma gondiiIL-18 binding proteinEndogenous IL-18Exogenous IL-18Cell-mediated pathologyPathological immune responsesProduction of IFNAnti-pathogen responsesCell productionInterleukin-18Immune pathologyImmune responseLymphoid cellsCell responsesInnate resistanceCD4IFNGondiiInfectionPathologyLimited roleInfection induces tissue-resident memory NK cells that safeguard tissue health
Schuster I, Sng X, Lau C, Powell D, Weizman O, Fleming P, Neate G, Voigt V, Sheppard S, Maraskovsky A, Daly S, Koyama M, Hill G, Turner S, O'Sullivan T, Sun J, Andoniou C, Degli-Esposti M. Infection induces tissue-resident memory NK cells that safeguard tissue health. Immunity 2023, 56: 531-546.e6. PMID: 36773607, PMCID: PMC10360410, DOI: 10.1016/j.immuni.2023.01.016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCytomegalovirus InfectionsHumansImmunity, InnateKiller Cells, NaturalMiceMuromegalovirusT-LymphocytesConceptsNK cellsTissue healthAdaptive-like featuresMemory NK cellsNatural killer cellsMurine cytomegalovirus infectionNon-lymphoid tissuesTissue-resident populationsCytomegalovirus infectionInnate cellsInnate lymphocytesKiller cellsAutoimmune diseasesTissue residencyImmune responseAdaptive immunityImmune equilibriumCardinal featuresSalivary glandsAdditional strategiesHealthCellsTissueCD4Response
2020
IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8
2019
Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells
Adams N, Geary C, Santosa E, Lumaquin D, Le Luduec J, Sottile R, van der Ploeg K, Hsu J, Whitlock B, Jackson B, Weizman O, Huse M, Hsu K, Sun J. Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells. Immunity 2019, 50: 1381-1390.e5. PMID: 31103381, PMCID: PMC6614060, DOI: 10.1016/j.immuni.2019.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytomegalovirusCytomegalovirus InfectionsCytotoxicity, ImmunologicGene Expression RegulationHerpesviridae InfectionsHost-Pathogen InteractionsHumansImmunologic MemoryKiller Cells, NaturalLymphocyte ActivationMiceMice, KnockoutMuromegalovirusNK Cell Lectin-Like Receptor Subfamily AT-Cell Antigen Receptor SpecificityConceptsNatural killer cellsNK cellsKiller cellsNK cell effector functionsMemory NK cellsNK cell poolHuman NK cellsCell effector functionsHuman CMV infectionCMV infectionCytomegalovirus infectionInnate lymphocytesAdaptive immunityAntiviral immunityEffector functionsRelevant antigensPreferential expansionHigh avidityCell avidityAntigen receptorCell poolAvidityAffinity maturationInfectionImmunity
2018
Epigenetic control of innate and adaptive immune memory
Lau C, Adams N, Geary C, Weizman O, Rapp M, Pritykin Y, Leslie C, Sun J. Epigenetic control of innate and adaptive immune memory. Nature Immunology 2018, 19: 963-972. PMID: 30082830, PMCID: PMC6225771, DOI: 10.1038/s41590-018-0176-1.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCD8-Positive T-LymphocytesCells, CulturedChromatinClonal Selection, Antigen-MediatedEpigenesis, GeneticGene Expression ProfilingHerpesviridae InfectionsImmunity, InnateImmunologic MemoryKiller Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutMuromegalovirusSTAT1 Transcription FactorSTAT4 Transcription FactorConceptsMammalian adaptive immune responseNK cellsDistinct epigenetic signaturesChromatin profilingAdaptive immune memoryAdaptive traitsEpigenetic controlTranscriptional statesNatural killer cellsT cell responsesAdaptive immune responsesEpigenetic modificationsEpigenetic signaturesTranscription factorsEpigenetic profilesInnate immune systemAccessibility stateRegulatory programsCanonical CD8Killer cellsImmunological memorySame infectionLymphocyte memoryT cellsImmune responseTranscription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response
Adams N, Lau C, Fan X, Rapp M, Geary C, Weizman O, Diaz-Salazar C, Sun J. Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response. Immunity 2018, 48: 1172-1182.e6. PMID: 29858012, PMCID: PMC6233715, DOI: 10.1016/j.immuni.2018.04.018.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsHerpesviridae InfectionsInterferon Regulatory FactorsKiller Cells, NaturalLymphocyte ActivationMiceMuromegalovirusConceptsNK cellsViral infectionAdaptive natural killer cell responsesVirus-specific NK cellsNatural killer cell responsesNK cell deficiencyNK cell functionNatural killer cellsNK cell proliferationSevere viral infectionsMouse cytomegalovirus (MCMV) infectionIRF8 mutationsTranscription factor STAT4Cytomegalovirus infectionInnate lymphocytesKiller cellsViral exposureCell deficiencyAdaptive immunityAntiviral immunityTranscription factor IRF8Cell responsesBiallelic mutationsViral susceptibilityInfection
2017
Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses
Rapp M, Lau C, Adams N, Weizman O, O'Sullivan T, Geary C, Sun J. Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses. Science Immunology 2017, 2 PMID: 29222089, PMCID: PMC6265048, DOI: 10.1126/sciimmunol.aan3796.Peer-Reviewed Original ResearchConceptsRunx transcription factorsTranscription factorsGene locusNK cellsTranscription factor signal transducerCell cycle programCore-binding factor βHistone mark H3K4me3Epigenetic controlAdaptive natural killer cell responsesChromatin immunoprecipitationEpigenetic modificationsClonal expansionNatural killer cell responsesSignal transducerPromoter regionMemory NK cellsNatural killer cellsNK cell activationTranscription 4Cycle programSpecific ablationInnate lymphocytesKiller cellsFactor βILC1 Confer Early Host Protection at Initial Sites of Viral Infection
Weizman O, Adams N, Schuster I, Krishna C, Pritykin Y, Lau C, Degli-Esposti M, Leslie C, Sun J, O’Sullivan T. ILC1 Confer Early Host Protection at Initial Sites of Viral Infection. Cell 2017, 171: 795-808.e12. PMID: 29056343, PMCID: PMC5687850, DOI: 10.1016/j.cell.2017.09.052.Peer-Reviewed Original ResearchConceptsImmune cellsViral infectionType 1 innate lymphoid cellsInitial antiviral responseInnate lymphoid cellsTissue-resident lymphocytesConventional dendritic cellsInnate immune cellsSite of infectionEarly antiviral immunityEarly host protectionViral burdenDendritic cellsViral loadProinflammatory cytokinesPrimary infectionAntiviral immunityHost protectionLymphoid cellsHost immunityInitial infectionAntiviral responseInfectionSTAT4-dependent mannerInitial site