2021
Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA
Ren X, Gelinas AD, Linehan M, Iwasaki A, Wang W, Janjic N, Pyle A. Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA. Journal Of Molecular Biology 2021, 433: 167227. PMID: 34487794, DOI: 10.1016/j.jmb.2021.167227.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, ViralAptamers, NucleotideBinding SitesCloning, MolecularCrystallography, X-RayDEAD Box Protein 58Escherichia coliGene ExpressionGenetic VectorsHumansImmunologic FactorsKineticsModels, MolecularMolecular MimicryMutationNucleic Acid ConformationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsReceptors, ImmunologicRecombinant ProteinsRNA, ViralSELEX Aptamer TechniqueConceptsHigh-resolution crystal structuresResolution crystal structureRIG-I receptorResult of mutationsSame amino acidsVertebrate organismsProtein receptorsInnate immune receptorsRNA virusesImmune receptorsAmino acidsTool compoundsViral ligandsViral RNAImportant receptorPathogenic moleculesGeneralizable strategyDNA aptamersMolecular mimicryCentral roleDisease statesReceptorsTerminusRNAOrganismsAntibodies 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 bloodErythematosusNeutrophilsPhagocytosisSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
2020
Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor
Kim DJ, Venkataraman A, Jain PC, Wiesler EP, DeBlasio M, Klein J, Tu SS, Lee S, Medzhitov R, Iwasaki A. Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 15837-15845. PMID: 32571957, PMCID: PMC7355044, DOI: 10.1073/pnas.2006949117.Peer-Reviewed Original ResearchConceptsAryl hydrocarbon receptorMethylation of DNAHuman cancer samplesHydrocarbon receptorAhR transcriptional activityAhR target genesFA deficiencyOne-carbon cycleAhR agonistsFolic acid functionAhR nuclear localizationLower transcriptionNuclear localizationTarget genesGene inductionHigher transcriptionTranscriptional activityXRE bindingDe novo generationCycle proteinsBirth defectsErythroid progenitorsFas functionMolecular levelFA uptakem6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development
Gao Y, Vasic R, Song Y, Teng R, Liu C, Gbyli R, Biancon G, Nelakanti R, Lobben K, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA, Li HB, Tebaldi T, Halene S. m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development. Immunity 2020, 52: 1007-1021.e8. PMID: 32497523, PMCID: PMC7408742, DOI: 10.1016/j.immuni.2020.05.003.Peer-Reviewed Original ResearchConceptsDouble-stranded RNADeleterious innate immune responseMammalian hematopoietic developmentEndogenous double-stranded RNAHematopoietic developmentInnate immune responseAbundant RNA modificationMurine fetal liverPattern recognition receptor pathwaysImmune responseProtein codingDsRNA formationRNA modificationsWriter METTL3Hematopoietic defectsPerinatal lethalityNative stateConditional deletionAberrant innate immune responsesLoss of METTL3Hematopoietic failureReceptor pathwayAberrant immune responsePrevents formationFetal liver
2018
An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication
Orzalli MH, Smith A, Jurado KA, Iwasaki A, Garlick JA, Kagan JC. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Molecular Cell 2018, 71: 825-840.e6. PMID: 30100266, PMCID: PMC6411291, DOI: 10.1016/j.molcel.2018.07.009.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsIL-1Host-derived damage-associated molecular patternsViral replicationVirus replicationInfected cellsInterleukin-1 family cytokinesIL-1 Signaling PathwayInflammatory gene expressionIL-1 actsHuman skin explantsProtective immunityIL-1αBarrier defenseInflammatory signalsViral infectionFamily cytokinesSkin explantsGene expressionMolecular patternsSkin fibroblastsSignaling pathwaysAntiviral systemBarrier epitheliaCell types
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 response
2000
Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine
Iwasaki A, Kelsall B. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine. Journal Of Experimental Medicine 2000, 191: 1381-1394. PMID: 10770804, PMCID: PMC2193144, DOI: 10.1084/jem.191.8.1381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChemokine CCL19Chemokine CCL20Chemokines, CCChemotaxisDendritic CellsDNA PrimersFemaleGene ExpressionIn Situ HybridizationMacrophage Inflammatory ProteinsMiceMice, Inbred BALB CMicroscopy, ConfocalModels, BiologicalPeyer's PatchesReceptors, CCR6Receptors, CCR7Receptors, ChemokineRNA, MessengerSpleenConceptsDendritic cell subsetsInterfollicular regionsDC subsetsCell subsetsInflammatory proteinPeyer's patchesSecondary lymphoid organ chemokineChemokine macrophage inflammatory proteinSplenic DC subsetsSubepithelial dome regionDistinct dendritic cell subsetsRole of chemokinesT cell responsesMacrophage inflammatory proteinT-cell regionsFollicle-associated epitheliumMurine Peyer's patchesTranscriptase-polymerase chain reaction analysisFunctional CCR7Lymphoid DCsMIP-3βPP DCsMyeloid DCsCCR7 expressionPolymerase chain reaction analysis