2008
Cutting Edge: Engagement of NKG2A on CD8+ Effector T Cells Limits Immunopathology in Influenza Pneumonia
Zhou J, Matsuoka M, Cantor H, Homer R, Enelow RI. Cutting Edge: Engagement of NKG2A on CD8+ Effector T Cells Limits Immunopathology in Influenza Pneumonia. The Journal Of Immunology 2008, 180: 25-29. PMID: 18096998, DOI: 10.4049/jimmunol.180.1.25.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensCD8-Positive T-LymphocytesHistocompatibility Antigens Class IInfluenza A virusMiceMice, Inbred BALB CMice, Inbred C57BLNK Cell Lectin-Like Receptor Subfamily CNK Cell Lectin-Like Receptor Subfamily DOrthomyxoviridae InfectionsPneumonia, ViralReceptors, ImmunologicReceptors, Natural Killer CellConceptsInfluenza pneumoniaT cellsLung injuryTNF productionT cell-mediated clearanceQa-1bAg-specific CD8Considerable lung injurySevere influenza infectionCD94/NKG2AT cell Ag recognitionEffector cell recognitionLimit immunopathologyNKG2A blockadeAntiviral CD8Distal airwaysInfluenza infectionPulmonary pathologyTNF-alphaCD8Infectious virusAg recognitionImmunopathologyPneumoniaCell recognition
2007
Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma
Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma. The Journal Of Immunology 2007, 178: 6191-6199. PMID: 17475846, DOI: 10.4049/jimmunol.178.10.6191.Peer-Reviewed Original ResearchConceptsHouse dust miteAirway epitheliumAllergic inflammationRole of STAT3Murine modelNovel asthma therapiesSignificant decreaseSTAT3 activationTh2 cell recruitmentAcute phase responseWild-type animalsAirway hyperresponsivenessAirway eosinophiliaAirway inflammationAllergic asthmaAsthma therapyChronic asthmaLung inflammationC57BL/6 miceAllergic responsesDust miteEpithelial STAT3Immune cellsSmooth muscleSTAT3 transcription factorA Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract
Niu N, Le Goff MK, Li F, Rahman M, Homer RJ, Cohn L. A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract. The Journal Of Immunology 2007, 178: 3846-3855. PMID: 17339484, DOI: 10.4049/jimmunol.178.6.3846.Peer-Reviewed Original ResearchConceptsAirway inflammationInflammatory diseasesRespiratory tractTh2-induced airway inflammationChronic airway inflammatory diseaseLymphocyte-deficient miceState of immunosuppressionAcute airway inflammationAirway inflammatory diseasesEffector Th cellsTh2 cells resultsAirway hyperresponsivenessInflammation wanesTh2 modelEffector Th1Respiratory illnessTh cellsInhalational exposureInflammationInhibitory effectSuch diseasesDiseaseStriking inhibitionTh1Localized treatment
2006
Genetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung
Lee CG, Cho S, Homer RJ, Elias JA. Genetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung. Annals Of The American Thoracic Society 2006, 3: 476a-477. PMID: 16921114, DOI: 10.1513/pats.200603-040ms.Peer-Reviewed Original ResearchIFN-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 ResearchAdenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis
Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W, Flavell RA, Boyden L, Lifton RP, Sun CX, Young HW, Elias JA. Adenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis. Journal Of Clinical Investigation 2006, 116: 1274-1283. PMID: 16670768, PMCID: PMC1451205, DOI: 10.1172/jci26372.Peer-Reviewed Original ResearchConceptsIL-4C57BL/6 miceBALB/cAirway fibrosisEosinophilic inflammationAdenosine metabolismEmphysematous alveolar destructionTissue adenosine levelsAdenosine receptor expressionIL-4 inducesAdenosine deaminase activityAlveolar destructionTh1 cytokinesC57BL/6 animalsEmphysematous destructionAdenosine levelsReceptor expressionTg animalsMurine lungMetalloproteinase-2Alveolar remodelingTissue inhibitorFibrosisInflammationPremature death
2005
Inhibition of the Src and Jak Kinases Protects against Lipopolysaccharide-induced Acute Lung Injury
Severgnini M, Takahashi S, Tu P, Perides G, Homer RJ, Jhung JW, Bhavsar D, Cochran BH, Simon AR. Inhibition of the Src and Jak Kinases Protects against Lipopolysaccharide-induced Acute Lung Injury. American Journal Of Respiratory And Critical Care Medicine 2005, 171: 858-867. PMID: 15665321, DOI: 10.1164/rccm.200407-981oc.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsCapillary Leak SyndromeEnzyme ActivationEnzyme InhibitorsEscherichia coliGene Expression RegulationGene Transfer TechniquesIndolesJanus Kinase 2LipopolysaccharidesLungMiceMice, Inbred BALB CProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeSignal TransductionSrc-Family KinasesSulfonamidesTranscriptional ActivationTyrphostinsConceptsAcute lung injuryLung injuryCytokine productionLPS challengeSmall molecule inhibitorsLipopolysaccharide-induced acute lung injuryLethal LPS challengeLung cytokine productionSystemic cytokine productionSelective tyrosine kinase inhibitorLung vascular permeabilityMurine lung injuryTyrosine kinase inhibitorsNovel therapeutic agentsMolecule inhibitorsSuppressor of cytokineChemokine productionSystemic inhibitionAirway epitheliumVascular permeabilitySpecific small molecule inhibitorsInjurySrc kinaseTherapeutic agentsKinase inhibitors
2004
Airway hyper‐reactivity mediated by B‐1 cell immunoglobulin M antibody generating complement C5a at 1 day post‐immunization in a murine hapten model of non‐atopic asthma
Kawikova I, Paliwal V, Szczepanik M, Itakura A, Fukui M, Campos RA, Geba GP, Homer RJ, Iliopoulou BP, Pober JS, Tsuji RF, Askenase PW. Airway hyper‐reactivity mediated by B‐1 cell immunoglobulin M antibody generating complement C5a at 1 day post‐immunization in a murine hapten model of non‐atopic asthma. Immunology 2004, 113: 234-245. PMID: 15379984, PMCID: PMC1782564, DOI: 10.1111/j.1365-2567.2004.01936.x.Peer-Reviewed Original ResearchConceptsAirflow obstructionImmune cellsC5a receptor-deficient miceSubsequent airway challengeNon-atopic asthmaReceptor-deficient miceImmunoglobulin M antibodiesIgM-producing cellsWild-type miceIgM monoclonal antibodyAirway reactivityHapten challengeHapten modelAirway challengeMethacholine challengeAsthma modelSkin immunizationLymph nodesNaive miceNaïve recipientsM antibodiesDays postimmunizationSubsequent airwayMale miceComplement C5aActivation of the STAT pathway in acute lung injury
Severgnini M, Takahashi S, Rozo LM, Homer RJ, Kuhn C, Jhung JW, Perides G, Steer M, Hassoun PM, Fanburg BL, Cochran BH, Simon AR. Activation of the STAT pathway in acute lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2004, 286: l1282-l1292. PMID: 14729509, DOI: 10.1152/ajplung.00349.2003.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHydrochloric AcidInterleukin-6Janus Kinase 2KineticsLipopolysaccharidesLiverLungMaleMiceMice, Inbred BALB CMice, Inbred C57BLMitogen-Activated Protein KinasesOxidation-ReductionPancreatitisProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeRespiratory MucosaSrc-Family KinasesSTAT3 Transcription FactorTrans-ActivatorsTumor Necrosis Factor-alphaConceptsAcute lung injuryIL-6Lung injuryLPS treatmentDevastating clinical problemGastric acid aspirationIntranasal LPS administrationResident lung cellsSTAT3 activationAcute pancreatitis modelSTAT activationAcid aspirationLPS administrationCytokine responsesInflammatory cellsInflammatory responsePancreatitis modelClinical problemMultiple organsLungLung cellsLPSEndothelial cellsTranscription factorsCritical mediator
2002
Interleukin-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
Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation
Wang J, Homer R, Chen Q, Elias J. Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation. The Journal Of Immunology 2000, 165: 4051-4061. PMID: 11034416, DOI: 10.4049/jimmunol.165.7.4051.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAerosolsAllergensAnimalsBronchial HyperreactivityChemokinesCytokinesGene Expression RegulationInflammationInterleukin-6LungMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, KnockoutMice, TransgenicOvalbuminPlethysmography, Whole BodyPulmonary EosinophiliaRNA, MessengerTh2 CellsVascular Cell Adhesion Molecule-1ConceptsIL-6Wild-type miceIL-13 proteinTh2 inflammationBronchoalveolar lavageIL-4IL-5IFN-gammaSensitized wild-type miceIL-6-deficient miceMonocyte chemoattractant protein-1Exaggerated airway responseTh2-dominated inflammationBALB/c backgroundInflammatory protein-1alphaChemoattractant protein-1IL-6 productionExogenous IL-6Endothelial VCAM-1Airway responsesAirway responsivenessAsthmatic airwaysExaggerated inflammationDeficient miceVCAM-1IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production
Wang J, Homer R, Hong L, Cohn L, Lee C, Jung S, Elias J. IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production. The Journal Of Immunology 2000, 165: 2222-2231. PMID: 10925310, DOI: 10.4049/jimmunol.165.4.2222.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAerosolsAllergensAnimalsBronchoalveolar Lavage FluidCytokinesGene Expression RegulationHumansImmunizationInterleukin-11MiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, TransgenicMucinsMucusOvalbuminPulmonary EosinophiliaRecombinant ProteinsRespiratory MucosaSpecies SpecificityTh2 CellsTurkeysVascular Cell Adhesion Molecule-1ConceptsTh2 cell accumulationIL-11OVA challengeMucus hypersecretionIL-4IL-5VCAM-1Cell accumulationMucin 5AC (MUC5AC) gene expressionVCAM-1 gene expressionAg-specific IgEBronchoalveolar lavage (BAL) inflammationLung IL-4Th2 cytokine productionIFN-gamma productionEndothelial-cell VCAM-1IL-13 mRNAIL-13 proteinChemoattractant protein 2Chemoattractant protein-3Mucus metaplasiaTh1 inflammationPulmonary eosinophiliaTh2 inflammationAirway inflammation
1999
Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils.
Cohn L, Homer RJ, MacLeod H, Mohrs M, Brombacher F, Bottomly K. Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils. The Journal Of Immunology 1999, 162: 6178-83. PMID: 10229862, DOI: 10.4049/jimmunol.162.10.6178.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAnimalsAsthmaBronchiEosinophiliaEosinophilsInterleukin-13 Receptor alpha1 SubunitInterleukin-4Interleukin-5Mast CellsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicMucusOvalbuminReceptors, InterleukinReceptors, Interleukin-13Receptors, Interleukin-4Th2 CellsConceptsMucus productionTh2 cellsAirway eosinophiliaAirway inflammationIL-4RalphaAirway mucus productionCD4 Th2 cellsAirway obstructionBAL eosinophiliaHuman asthmaticsMucus hyperproductionClinical symptomsIL-13Recipient miceTh1 cellsIL-4IL-5Respiratory tractEosinophiliaMast cellsAnimal modelsEosinophilsMarked increaseCell stimulationMucus
1997
Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production
Cohn L, Homer R, Marinov A, Rankin J, Bottomly K. Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production. Journal Of Experimental Medicine 1997, 186: 1737-1747. PMID: 9362533, PMCID: PMC2199146, DOI: 10.1084/jem.186.10.1737.Peer-Reviewed Original ResearchConceptsTh2 cellsMucus productionAirway inflammationIL-4Asthmatic patientsCell recruitmentOVA-specific Th2 cellsT helper 2 cellsIL-4-deficient miceAirway mucus productionOVA-specific TCRRole of Th1CD4 T cellsImportant clinical symptomInduction of inflammationTh2 cell recruitmentCD4 Th1Airway biopsiesClinical symptomsTh1 cellsTNF-alphaT cellsInterleukin-4Effector functionsMucus secretion