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 expressionAdipokinesObesityIFN
2021
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophagesAntibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus
Tokuyama M, Gunn BM, Venkataraman A, Kong Y, Kang I, Rakib T, Townsend MJ, Costenbader KH, Alter G, Iwasaki A. Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus. Journal Of Experimental Medicine 2021, 218: e20191766. PMID: 34019642, PMCID: PMC8144942, DOI: 10.1084/jem.20191766.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusNeutrophil extracellular trapsLupus erythematosusImmune complexesFormation of NETsEnvelope proteinSLE patient bloodInnate immune activationImmune complex formationActivate neutrophilsInterferon statusAutoantibody levelsIgG levelsHigher interferonImmune activationNeutrophil phagocytosisSLE IgGNeutrophil activationExtracellular trapsSLE plasmaNeutrophil elastasePatient's bloodErythematosusNeutrophilsPhagocytosis
2020
Interferon deficiency can lead to severe COVID
Meffre E, Iwasaki A. Interferon deficiency can lead to severe COVID. Nature 2020, 587: 374-376. PMID: 33139913, DOI: 10.1038/d41586-020-03070-1.Peer-Reviewed Original ResearchType I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19
Park A, Iwasaki A. Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19. Cell Host & Microbe 2020, 27: 870-878. PMID: 32464097, PMCID: PMC7255347, DOI: 10.1016/j.chom.2020.05.008.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Role of interferonType ICoronavirus disease 2019COVID-19Innate antiviral responseOngoing global threatCoronavirus 2Pathogenic coronavirusesTreatment strategiesDisease 2019Protective effectHuman coronavirusesRecombinant interferonMERS-CoVSARS-CoVAntiviral responseInterferonAntiviral therapeuticsCombat COVID-19Interferon inductionGlobal pandemicCutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy.
Gopinath S, Lu P, Iwasaki A. Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy. The Journal Of Immunology 2020, 204: 1703-1707. PMID: 32122994, DOI: 10.4049/jimmunol.1900462.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsGenital herpes infectionMemory T cellsT cellsHerpes infectionVirus-specific effector T cellsVaginal applicationTopical vaginal applicationCD8 T cellsEffector T cellsProtective immune responseSingle topical applicationTopical aminoglycosidesGenital mucosaChemokine expressionVaccine strategiesImmune responseVaginal mucosaTopical applicationBarrier tissuesMiceRobust activationAminoglycoside antibioticsMucosaInfection
2018
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development
Yockey LJ, Iwasaki A. Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development. Immunity 2018, 49: 397-412. PMID: 30231982, PMCID: PMC6152841, DOI: 10.1016/j.immuni.2018.07.017.Peer-Reviewed Original ResearchConceptsFetal developmentHealthy pregnancyImmune responseFetal immune responseRole of interferonPregnancy complicationsProinflammatory cytokinesSuccessful pregnancyCertain infectionsPregnant mothersImmune cellsInflammatory conditionsSevere diseasePregnancyFetal diseaseImmune systemCytokinesCongenital disorderPossible targetsInterferonFetusesInfectionDiseaseMothersComplicationsKDM5 histone demethylases repress immune response via suppression of STING
Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, Shadel GS, Yan Q. KDM5 histone demethylases repress immune response via suppression of STING. PLOS Biology 2018, 16: e2006134. PMID: 30080846, PMCID: PMC6095604, DOI: 10.1371/journal.pbio.2006134.Peer-Reviewed Original ResearchConceptsImmune responseSTING expressionCyclic GMP-AMP synthase stimulatorSuppression of STINGCancer cellsCancer immunotherapy agentsHuman papilloma virusAdaptive immune responsesMultiple clinical trialsExpression of STINGBreast cancer cellsInnate immune defenseRobust interferon responseMultiple cancer typesIntratumoral CD8Immunotherapy agentsAnticancer immunotherapyPatient survivalNeck cancerPapilloma virusClinical trialsT cellsSTING agonistsKDM5 histonePositive headA minimal RNA ligand for potent RIG-I activation in living mice
Linehan MM, Dickey TH, Molinari ES, Fitzgerald ME, Potapova O, Iwasaki A, Pyle AM. A minimal RNA ligand for potent RIG-I activation in living mice. Science Advances 2018, 4: e1701854. PMID: 29492454, PMCID: PMC5821489, DOI: 10.1126/sciadv.1701854.Peer-Reviewed Original ResearchConceptsStem-loop RNAInterferon-stimulated genesImmune systemPotent synthetic activatorVertebrate immune systemType I interferonInnate immune systemRIG-I receptorRIG-I activationExpression networksRemodeling factorsPotent RIGRNA sequencingSpecific genesRNA ligandsI interferonAntiviral defenseInterferon responseRNA sensorsPolycytidylic acidSynthetic activatorsMiceInterferonGenesRNA
2017
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonOlder adultsIFN inductionRetinoic acid-inducible gene IAcid-inducible gene IHealthy human donorsType I interferonRespiratory influenzaProinflammatory cytokinesVirus infectionType I IFN genesAdult monocytesAntiviral resistanceTranscription factor IRF8IFN responseHuman donorsMonocytesIncreased proteasomal degradationHuman monocytesYoung adultsIRF8 expressionIAV RNAInfected cellsImmune Regulation of Antibody Access to Neuronal Tissues
Iwasaki A. Immune Regulation of Antibody Access to Neuronal Tissues. Trends In Molecular Medicine 2017, 23: 227-245. PMID: 28185790, PMCID: PMC5626569, DOI: 10.1016/j.molmed.2017.01.004.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBlood-nerve barrierAdaptive immune systemImmune systemAntibody accessInnate immune controlUse of vaccinesImmune controlNeurotropic virusesCancer immunotherapyImmune regulationImmune surveillanceT cellsTAM receptorsNeurodegenerative conditionsAlzheimer's diseaseNeuronal tissueNeural tissueDiseaseTissueNovel insightsSuch novel insightsImmunotherapyCD4Cells
2016
Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature
Foxman EF, Storer JA, Vanaja K, Levchenko A, Iwasaki A. Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8496-8501. PMID: 27402752, PMCID: PMC4968739, DOI: 10.1073/pnas.1601942113.Peer-Reviewed Original ResearchConceptsIFN-independent mechanismsEpithelial cellsHost defense strategiesHost cell deathIFN inductionHuman bronchial epithelial cellsReduced virus productionCommon cold virusInfected epithelial cellsB-cell lymphoma 2 (Bcl-2) overexpressionBronchial epithelial cellsDiverse stimuliViral replicationAntiviral pathwaysCell deathH1-HeLa cellsTemperature-dependent replicationCell typesSingle replication cycleTemperature-dependent growthReplication cycleWarmer temperaturesCool temperaturesDefense strategiesType 1 IFN responseO-linked sugars sound the alarm
Gopinath S, Kumamoto Y, Iwasaki A. O-linked sugars sound the alarm. Nature Immunology 2016, 17: 119-120. PMID: 26784258, DOI: 10.1038/ni.3364.Peer-Reviewed Original Research
2013
Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses
Mattei LM, Cotmore SF, Li L, Tattersall P, Iwasaki A. Toll-Like Receptor 9 in Plasmacytoid Dendritic Cells Fails To Detect Parvoviruses. Journal Of Virology 2013, 87: 3605-3608. PMID: 23302877, PMCID: PMC3592163, DOI: 10.1128/jvi.03155-12.Peer-Reviewed Original Research