2023
IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury.
Sun Y, Hu B, Stanley G, Harris ZM, Gautam S, Homer R, Koff JL, Rajagopalan G. IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2023, 68: 75-89. PMID: 36125351, PMCID: PMC9817908, DOI: 10.1165/rcmb.2022-0117oc.Peer-Reviewed Original ResearchConceptsCytokine release syndromeAcute lung injuryExtrapulmonary acute lung injuryIFN-γ KO miceIL-17ALung injuryKO miceStaphylococcal enterotoxin BRelease syndromeIL-17A KO miceSevere acute lung injuryAcute respiratory distress syndromeSystemic T cell activationEnterotoxin BAdaptive T lymphocytesDR3 transgenic miceNeutralization of IFNRespiratory distress syndromeHuman leukocyte antigenRole of IFNT cell cytokinesJanus kinase inhibitorS100A8/A9T cell activationALI parameters
2014
An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection
Lafferty EI, Flaczyk A, Angers I, Homer R, d'Hennezel E, Malo D, Piccirillo CA, Vidal SM, Qureshi ST. An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection. Genes & Immunity 2014, 15: 320-332. PMID: 24848930, PMCID: PMC4978536, DOI: 10.1038/gene.2014.22.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsCD8-Positive T-LymphocytesChemokine CXCL10EndosomesEthylnitrosoureaImmunity, InnateInfluenza A Virus, H1N1 SubtypeInterferon Type IInterferon-gammaL-SelectinLungLymphocyte ActivationMacrophage ActivationMembrane Transport ProteinsMiceMice, Inbred C57BLMutationOrthomyxoviridae InfectionsToll-Like ReceptorsConceptsEndosomal TLRsImmune responseEndosomal Toll-like receptorsInfluenza A/PR/8/34Expression of CXCL10Toll-like receptorsImmune cell activationCD69 activation markerInnate immune responseHuman infectious diseasesViral clearanceActivation markersInfected lungsRespiratory pathogensTLR responsesT cellsLymphoid cellsCell activationTissue pathologyInfectious diseasesMouse strainsInfectionExudate macrophagesReduced expressionUNC93B1
2013
Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway
Choo-Wing R, Syed MA, Harijith A, Bowen B, Pryhuber G, Janér C, Andersson S, Homer RJ, Bhandari V. Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 749-757. PMID: 23470621, PMCID: PMC3727872, DOI: 10.1165/rcmb.2012-0381oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBronchopulmonary DysplasiaCelecoxibCell DeathCyclooxygenase 2Cyclooxygenase 2 InhibitorsEndoplasmic Reticulum StressHumansHyperoxiaImmunohistochemistryInfant, NewbornInterferon-gammaLungMiceMice, Inbred C57BLMice, TransgenicPyrazolesRNA, Small InterferingSulfonamidesTranscription Factor CHOPConceptsBronchopulmonary dysplasiaCyclooxygenase-2Endoplasmic reticulum stress-dependent pathwaysER stress pathway activationPathway mediatorsHuman bronchopulmonary dysplasiaFinal common pathwayAlveolar epithelial cellsImpaired alveolarizationStress pathway activationCOX2 inhibitionMurine modelMurine lungClinical relevanceIFNVivo modelHyperoxiaLungHuman lungPathway activationCHOP siRNAStress-dependent pathwaysInjuryEpithelial cellsCommon pathway
2011
IFN-γ Acts on the Airway Epithelium To Inhibit Local and Systemic Pathology in Allergic Airway Disease
Mitchell C, Provost K, Niu N, Homer R, Cohn L. IFN-γ Acts on the Airway Epithelium To Inhibit Local and Systemic Pathology in Allergic Airway Disease. The Journal Of Immunology 2011, 187: 3815-3820. PMID: 21873527, PMCID: PMC3178669, DOI: 10.4049/jimmunol.1100436.Peer-Reviewed Original ResearchConceptsAirway epitheliumAllergic airway inflammationAllergic airway diseaseTh2 cell activationGoal of therapyProduction of IFNAdministration of medicationsSystemic side effectsAirway mucosal surfaceAirway epithelial cellsSites of inflammationIFN-γ actionAirway inflammationAirway obstructionPersistent asthmaRefractory asthmaAirway diseaseIFN-γRTh1 cellsPathological responseSystemic pathologyEffector functionsSide effectsBone marrowAsthmaA Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs
Harijith A, Choo-Wing R, Cataltepe S, Yasumatsu R, Aghai ZH, Janér J, Andersson S, Homer RJ, Bhandari V. A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs. American Journal Of Respiratory Cell And Molecular Biology 2011, 44: 621-630. PMID: 21216975, PMCID: PMC3095982, DOI: 10.1165/rcmb.2010-0058oc.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaHuman bronchopulmonary dysplasiaLung architectureRole of IFNγMatrix metalloproteinase-9Caspase-3Final common pathwayMatrix metalloproteinases 2Downstream targetsImpaired alveolarizationLung injuryChemokine ligandMetalloproteinase-9IFNγ mRNAAngiopoietin-2Murine modelLittermate controlsPulmonary phenotypeMurine lungClinical relevanceLung phenotypeAngiopoietin-1IFNγMetalloproteinases 2Lung
2009
Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation
Niu N, Laufer T, Homer RJ, Cohn L. Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation. The Journal Of Immunology 2009, 183: 1523-1527. PMID: 19596982, DOI: 10.4049/jimmunol.0901349.Peer-Reviewed Original ResearchConceptsAllergic airway inflammationMHC class II expressionAirway inflammationDendritic cellsClass II expressionTh2 generationTh2 immunityTh2-dependent allergic airway inflammationTh1 immune responseIFN-gamma productionAirway neutrophiliaTh2 primingRespiratory tractTh2 cellsImmune responseClass II signalsInflammationTh2 recruitmentMice resultsMiceCells altersImmunityActivationCellsNeutrophilia
2006
IFN-γ–dependent DNA Injury and/or Apoptosis Are Critical in Cigarette Smoke–induced Murine Emphysema
Kang MJ, Lee CG, Cho SJ, Homer RJ, Elias JA. IFN-γ–dependent DNA Injury and/or Apoptosis Are Critical in Cigarette Smoke–induced Murine Emphysema. Annals Of The American Thoracic Society 2006, 3: 517a-518. PMID: 16921135, DOI: 10.1513/pats.200603-075ms.Peer-Reviewed Original ResearchState of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease
Elias JA, Kang MJ, Crothers K, Homer R, Lee CG. State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease. Annals Of The American Thoracic Society 2006, 3: 494-498. PMID: 16921126, DOI: 10.1513/pats.200603-068ms.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseVascular endothelial growth factorSecretory leukocyte proteinase inhibitorTh1/Tc1Obstructive pulmonary diseaseAlveolar destructionIFN-gammaMatrix metalloproteinasesMucus metaplasiaPulmonary diseaseCCR5-dependent mechanismEmphysematous alveolar destructionCigarette smoke exposureCytokine IFN-gammaIFN-gamma responsesEndothelial growth factorApoptosis-independent pathwayCCR5/Pulmonary fibrosisPulmonary responseSmoke exposureIL-13CC chemokinesFibrotic responseMurine lung
2005
Role of CCR5 in IFN-γ–induced and cigarette smoke–induced emphysema
Ma B, Kang MJ, Lee CG, Chapoval S, Liu W, Chen Q, Coyle AJ, Lora JM, Picarella D, Homer RJ, Elias JA. Role of CCR5 in IFN-γ–induced and cigarette smoke–induced emphysema. Journal Of Clinical Investigation 2005, 115: 3460-3472. PMID: 16284650, PMCID: PMC1280966, DOI: 10.1172/jci24858.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnnexin A5ApoptosisBronchoalveolar LavageCell DeathChemokinesDNADNA PrimersEmphysemaEnzyme-Linked Immunosorbent AssayFemaleImmunohistochemistryIn Situ Nick-End LabelingInflammationInterferon-gammaLigandsLungMacrophagesMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, TransgenicMutationPhenotypePulmonary AlveoliReceptors, CCR5Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerSmokingTime FactorsConceptsCCR5 ligandsIFN-gammaPotent stimulatorCigarette smoke-induced inflammationCigarette smoke-induced emphysemaSecretory leukocyte protease inhibitorImportance of CCR5Murine emphysema modelPathogenesis of IFNRANTES/CCLSmoke-induced inflammationDNA injuryRole of CCR5Smoke-induced emphysemaLeukocyte protease inhibitorSelect chemokinesTh1 inflammationPulmonary inflammationEmphysema modelCXC chemokinesTissue destructionIFN-gamma stimulationMMP-9CCR5Cigarette smokeRole of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema
Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, DeSanctis G, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema. The Journal Of Immunology 2005, 174: 8106-8115. PMID: 15944319, DOI: 10.4049/jimmunol.174.12.8106.Peer-Reviewed Original ResearchConceptsNull mutationEpithelial cell apoptosisCell apoptosisDNA injuryTissue remodelingProtease accumulationCaspase inhibitorsMitochondrial apoptosis pathway activationDeath receptorsPropidium iodide stainingCathepsin SHuman diseasesApoptosis responseApoptosis pathway activationApoptosis inhibitionCaspase-3ApoptosisIodide stainingPathway activationCathepsin S inhibitionMutationsRemodelingCritical eventsAlveolar remodelingIFN-gamma
2004
Regulation of pulmonary fibrosis by chemokine receptor CXCR3
Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, Fan J, Gao Y, Yin Z, Homer R, Gerard C, Noble PW. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. Journal Of Clinical Investigation 2004, 114: 291-299. PMID: 15254596, PMCID: PMC449741, DOI: 10.1172/jci16861.Peer-Reviewed Original ResearchConceptsCXC chemokine receptor 3Lung NK cellsCXCR3-deficient miceIFN-gamma productionLung injuryIFN-gammaEnhanced fibrosisNK cellsWT miceChemokine receptors CXC chemokine receptor 3Chemokine MIG/CXCL9Endogenous IFN-gamma productionI-TAC/CXCL11IP-10/CXCL10Inflammatory cell recruitmentProgressive interstitial fibrosisChemokine receptor 3Exogenous IFN-gammaExpression of CXCL10MIG/CXCL9CXCR3 deficiencyAdoptive transferPulmonary injuryLymph nodesPulmonary fibrosis
2003
Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro
Zheng T, Zhu Z, Liu W, Lee CG, Chen Q, Homer RJ, Elias JA. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro. Journal Of Allergy And Clinical Immunology 2003, 111: 720-728. PMID: 12704349, DOI: 10.1067/mai.2003.1383.Peer-Reviewed Original ResearchConceptsIL-13Ralpha1 mRNAIL-13IL-13Ralpha2IL-13Ralpha1IL-4IFN-gammaRegulatory eventsTransgenic IL-13Epithelial cellsIL-13 responsesMRNA accumulationAirway epithelial cellsSites of inflammationIL-13 signalsIL-13 stimulationHigh-affinity receptorIL-10Lung fragmentsControl miceOverexpression miceIL-13Rα2Cytokine regulationIL-4RalphaIL-13Rα1Receptor subunits
2002
Cytokine Regulation of Mucus Production in a Model of Allergic Asthma
Cohn L, Whittaker L, Niu N, Homer RJ. Cytokine Regulation of Mucus Production in a Model of Allergic Asthma. Novartis Foundation Symposia 2002, 248: 201-220. PMID: 12568496, DOI: 10.1002/0470860790.ch13.BooksMeSH KeywordsAdministration, InhalationAnimalsAsthmaBronchoalveolar Lavage FluidCells, CulturedExocytosisGene Expression RegulationImmunizationInterferon-gammaInterferonsInterleukin-13Interleukin-13 Receptor alpha1 SubunitInterleukin-4Interleukin-5Interleukin-9Mast CellsMiceMice, TransgenicModels, AnimalMucinsMucusOvalbuminPeptide FragmentsPulmonary EosinophiliaRadiation ChimeraReceptors, Antigen, T-Cell, alpha-betaReceptors, InterleukinReceptors, Interleukin-13Receptors, Interleukin-4Respiratory SystemSignal TransductionTh1 CellsTh2 CellsConceptsAirway inflammationTh2 cellsMucus productionTh1 cellsT cell receptor transgenic CD4Airway inflammatory infiltrateDifferent lymphocyte subsetsBone marrow chimerasAbsence of interleukinAirway obstructionAllergic asthmaLymphocyte subsetsEosinophilic inflammationMucus hyperproductionInflammatory infiltrateClinical symptomsInflammatory cellsTh2 lymphocytesRecipient miceTh cellsTransgenic CD4Respiratory tractMast cellsCytokine regulationInflammationInterleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9
Whittaker L, Niu N, Temann U, Stoddard A, Flavell RA, Ray A, Homer RJ, Cohn L. Interleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9. American Journal Of Respiratory Cell And Molecular Biology 2002, 27: 593-602. PMID: 12397019, DOI: 10.1165/rcmb.4838.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCells, CulturedGene Expression RegulationInterferon-gammaInterleukin-13Interleukin-9LungMiceMice, Inbred BALB CMice, Mutant StrainsMice, TransgenicMucin 5ACMucinsNF-kappa BReceptors, InterferonReceptors, Interleukin-4Recombinant ProteinsRespiratory MucosaSignal TransductionTh2 CellsConceptsIL-13Th2 cellsTh2-induced airway inflammationEpithelial mucusCD4 Th cellsCD4 T cellsAbsence of interleukinIL-13 actsNuclear factor-kappaBAsthma resultsTh2 effectsAirway inflammationMucus hyperproductionNegative infectionsTh cytokinesInflammatory cellsRecipient miceTh cellsIL-4IL-5Respiratory tractAirway epitheliumIL-9T cellsComplete blockade
2001
IL-4 Promotes Airway Eosinophilia by Suppressing IFN-γ Production: Defining a Novel Role for IFN-γ in the Regulation of Allergic Airway Inflammation
Cohn L, Herrick C, Niu N, Homer R, Bottomly K. IL-4 Promotes Airway Eosinophilia by Suppressing IFN-γ Production: Defining a Novel Role for IFN-γ in the Regulation of Allergic Airway Inflammation. The Journal Of Immunology 2001, 166: 2760-2767. PMID: 11160342, DOI: 10.4049/jimmunol.166.4.2760.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, CutaneousAdministration, IntranasalAdoptive TransferAnimalsBone Marrow CellsBone Marrow TransplantationBronchiCell MovementDown-RegulationEosinophilsFemaleHematopoietic Stem CellsInflammationInterferon-gammaInterleukin-13Interleukin-4Interleukin-5MaleMiceMice, Inbred BALB CMice, KnockoutMice, TransgenicOvalbuminPulmonary EosinophiliaReceptors, InterferonRespiratory HypersensitivityTh2 CellsUp-RegulationConceptsAirway eosinophiliaIL-4IFN-gammaTh2 cellsAirway eosinophilsIL-5Allergic airway inflammationIFN-γ productionTh2 cell generationAirway inflammationEosinophilic inflammationLung eosinophiliaLung parenchymalTh2 cytokinesIntranasal administrationRespiratory tractLung tissueCounterregulatory effectsEosinophiliaCell transferEosinophilsHemopoietic cellsInflammationAirwayIFN
2000
Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung
Wang Z, Zheng T, Zhu Z, Homer R, Riese R, Chapman H, Shapiro S, Elias J. Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung. Journal Of Experimental Medicine 2000, 192: 1587-1600. PMID: 11104801, PMCID: PMC2193095, DOI: 10.1084/jem.192.11.1587.Peer-Reviewed Original ResearchConceptsAdult murine lungMurine lungProtease/antiprotease balanceChronic obstructive pulmonary diseaseSecretory leukocyte proteinase inhibitorNeutrophil-rich inflammationObstructive pulmonary diseaseInterferon γ inductionPulmonary diseasePulmonary complianceChronic inflammationInflammatory responseLung volumePulmonary emphysemaPulmonary tissueΓ inductionAlveolar enlargementMMP-9Matrix metalloproteinaseEmphysemaLungInflammationSelective inhibitionProminent proteaseMacrophages
1999
T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production
Cohn L, Homer R, Niu N, Bottomly K. T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production. Journal Of Experimental Medicine 1999, 190: 1309-1318. PMID: 10544202, PMCID: PMC2195688, DOI: 10.1084/jem.190.9.1309.Peer-Reviewed Original ResearchConceptsTh1 cellsTh2 cellsMucus productionAirway eosinophiliaIFN-gammaRecipient miceAirway inflammationIFN-gamma receptor signalingT helper type 1T helper 1 cellsAllergic airway inflammationTh2 cytokine secretionHelper type 1Different inhibitory pathwaysAsthmatic patientsPathologic featuresCytokine secretionInflammatory responseRespiratory tractEosinophiliaInhibitory pathwaysMouse modelInflammationType 1Marked reduction