2023
Infection 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 ResearchConceptsNK 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 CD8Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding
Weizman O, Krykbaeva I, Bosenburg M, Iwasaki A. Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding. The Journal Of Immunology 2020, 204: 88.17-88.17. DOI: 10.4049/jimmunol.204.supp.88.17.Peer-Reviewed Original ResearchConventional type 2 dendritic cellsType 2 dendritic cellsImmune cellsMetastatic burdenNK cellsDendritic cellsIntracardiac injectionHost anti-tumor immunityType I IFN-independent mannerAdaptive immune cellsAnti-tumor immunityLocal immune cellsNatural killer cellsSyngeneic mouse modelIFN-independent mannerEarly metastatic seedingMetastatic controlTranscription factor IRF3Killer cellsPrimary tumorMetastatic spreadInnate sensorsMouse modelMetastatic growthMetastatic seeding
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 maturationInfectionImmunityCytomegalovirus infection drives avidity selection of natural killer cells
Adams N, Lumaquin D, Santosa E, Whitlock B, Jackson B, Le Luduec J, Sottile R, Weizman O, Huse M, Hsu K, Sun J. Cytomegalovirus infection drives avidity selection of natural killer cells. The Journal Of Immunology 2019, 202: 76.3-76.3. DOI: 10.4049/jimmunol.202.supp.76.3.Peer-Reviewed Original ResearchNK cell poolNK cellsNatural killer cellsKiller cellsImmune responseNK cell effector functionsNK cell populationHuman NK cellsIFN-γ productionCell effector functionsCell poolSecondary immune responseAntiviral immune responseHuman CMV infectionGreater receptor affinityGreater clonal expansionCMV infectionCytomegalovirus infectionInnate lymphocytesAvidity maturationInfectious challengeMCMV infectionReceptor expressionVirus infectionEffector functions
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 ResearchConceptsNK 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 β
2016
Atg5 Is Essential for the Development and Survival of Innate Lymphocytes
O’Sullivan T, Geary C, Weizman O, Geiger T, Rapp M, Dorn G, Overholtzer M, Sun J. Atg5 Is Essential for the Development and Survival of Innate Lymphocytes. Cell Reports 2016, 15: 1910-1919. PMID: 27210760, PMCID: PMC4889506, DOI: 10.1016/j.celrep.2016.04.082.Peer-Reviewed Original ResearchConceptsInnate lymphocytesHomeostatic proliferationMature natural killer (NK) cellsInnate lymphoid cell developmentNatural killer cellsCell-intrinsic apoptosisLymphoreplete miceLymphoid cell developmentLymphocyte numbersKiller cellsMetformin treatmentLymphopenic hostsLymphocyte precursorsGroup 1Induction of autophagyLymphocyte survivalILC developmentInducible ablationLymphocytesLymphocyte developmentSurvivalCell developmentAutophagyATG5Cellular survival mechanism