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 marrowAsthma
2010
Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation
Wright PL, Yu J, Di YP, Homer RJ, Chupp G, Elias JA, Cohn L, Sessa WC. Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation. Journal Of Experimental Medicine 2010, 207: 2595-2607. PMID: 20975041, PMCID: PMC2989775, DOI: 10.1084/jem.20100786.Peer-Reviewed Original ResearchConceptsLung inflammationTh2-mediated lung inflammationSevere human asthmaAsthma-like phenotypeNonallergic miceHuman asthmaInflammation resultsKO miceLung tissueNogo expressionAirway epitheliumSmooth muscleReticulon 4BTransgenic miceLung epitheliumEpithelial reconstitutionMiceMarked reductionProtective genesEndogenous regulatorNogoInflammationLungPLUNCTransgenic expression
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 altersImmunityActivationCellsNeutrophiliaAdvances in Mucous Cell Metaplasia
Curran DR, Cohn L. Advances in Mucous Cell Metaplasia. American Journal Of Respiratory Cell And Molecular Biology 2009, 42: 268-275. PMID: 19520914, PMCID: PMC2830403, DOI: 10.1165/rcmb.2009-0151tr.BooksConceptsMucous cell metaplasiaCell metaplasiaMucous metaplasiaChronic obstructive pulmonary diseaseChronic airway diseasesObstructive pulmonary diseaseExacerbation of asthmaChronic airwayAirway obstructionAirway diseaseMucus hypersecretionPulmonary diseaseMolecular mechanismsHarmful insultsIL-13MUC5AC expressionEpidermal growth factor receptor (EGFR) activationGoblet cell granulesGrowth factor receptor activationMucin productionMucus productionNew therapiesGoblet cellsFront-line protectionMetaplasiaA sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma
Caceres AI, Brackmann M, Elia MD, Bessac BF, del Camino D, D'Amours M, Witek JS, Fanger CM, Chong JA, Hayward NJ, Homer RJ, Cohn L, Huang X, Moran MM, Jordt SE. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 9099-9104. PMID: 19458046, PMCID: PMC2684498, DOI: 10.1073/pnas.0900591106.Peer-Reviewed Original ResearchConceptsAsthmatic airway inflammationAirway inflammationAirway hyperreactivityAllergen challengeHC-030031Airway allergen challengeEndogenous TRPA1 agonistsMurine ovalbumin modelImpaired inflammatory responseTreatment of asthmaRole of TRPA1Wild-type miceAirway epithelial functionAllergic inflammatory conditionsPromising pharmacological targetNeuronal ion channelsLipid peroxidation productsIon channelsAllergic asthmaAirway exposureEosinophil infiltrationLeukocyte infiltrationContractile stimuliInflammatory disordersOvalbumin model
2007
A 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
2004
Asthma: Mechanisms of Disease Persistence and Progression
Cohn L, Elias JA, Chupp GL. Asthma: Mechanisms of Disease Persistence and Progression. Annual Review Of Immunology 2004, 22: 789-815. PMID: 15032597, DOI: 10.1146/annurev.immunol.22.012703.104716.BooksConceptsIL-13Key effector cytokineAnti-inflammatory therapyIL-13 productionProduction of chemokinesProgression of diseaseAirway fibrosisAllergic asthmaAirway remodelingEffector cytokinesEosinophilic inflammationPersistent diseaseTh2 cytokinesEpithelial damageDisease progressionInflammatory responseTh2 cellsMucus productionSmooth muscleBronchial airwaysMatrix metalloproteinasesAnimal dataAsthmaDisease persistenceInflammation
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 cellsInflammationAirwayIFNA critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation
Das J, Chen C, Yang L, Cohn L, Ray P, Ray A. A critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation. Nature Immunology 2001, 2: 45-50. PMID: 11135577, DOI: 10.1038/83158.Peer-Reviewed Original ResearchConceptsAllergic airway inflammationT helper 2GATA-3 expressionTh2 differentiationAirway inflammationGATA3 expressionAirway eosinophilic inflammationTh2 cytokine productionT-bet expressionInterferon-γ ProductionTh2 cell recruitmentTranscription factor GATA-3NF-κB activityNuclear factor κBT cell receptorEosinophilic inflammationHelper 2Asthma pathogenesisCytokine productionIL-13IL-5Th2 cellsT cellsInterleukin-4Cell recruitment
2000
T-helper type 2 cell-directed therapy for asthma
Cohn L, Ray A. T-helper type 2 cell-directed therapy for asthma. Pharmacology & Therapeutics 2000, 88: 187-196. PMID: 11150597, DOI: 10.1016/s0163-7258(00)00091-7.BooksConceptsTh2 cell differentiationT helper type 2 cellsNew immunomodulatory strategiesCell-directed therapiesChronic inflammatory diseaseTh2 cell functionType 2 cellsTh cell developmentImmunomodulatory strategiesPathophysiologic abnormalitiesInflammatory diseasesRespiratory tractTh2 cellsImmune responseTraditional therapiesCell differentiationBronchial airwaysAsthmaTherapyCell functionCell effectsCytokinesDiseaseCell developmentMolecular mechanismsIL-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
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 reductionInhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3
Zhang D, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A. Inhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3. Immunity 1999, 11: 473-482. PMID: 10549629, DOI: 10.1016/s1074-7613(00)80122-3.Peer-Reviewed Original ResearchMeSH KeywordsAerosolsAmino Acid SubstitutionAnimalsAsthmaBronchoalveolar Lavage FluidDNA-Binding ProteinsDrug HypersensitivityEosinophiliaGATA3 Transcription FactorGene Expression RegulationGenes, DominantImmunizationImmunoglobulin EInflammationInterleukin-13Interleukin-4Interleukin-5LungMiceMice, Inbred C57BLMice, TransgenicMucusMutagenesis, Site-DirectedOvalbuminTh2 CellsTrans-ActivatorsConceptsCytokines IL-4GATA-3IL-13IL-4IL-5Th2 cytokines IL-4Pathogenesis of asthmaTreatment of asthmaTranscription factor GATA-3Potential therapeutic targetAirway eosinophiliaTh2 responsesAllergic inflammationAllergic diseasesTh2 cytokinesT-cell-specific fashionTh1 cellsIgE synthesisTh2 cellsMucus productionMurine modelTherapeutic targetTransgenic miceAsthmaDominant negative mutant
1998
Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation
Yang L, Cohn L, Zhang D, Homer R, Ray A, Ray P. Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation. Journal Of Experimental Medicine 1998, 188: 1739-1750. PMID: 9802985, PMCID: PMC2212522, DOI: 10.1084/jem.188.9.1739.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAsthmaBase SequenceChemokine CCL11Chemokines, CCCytokinesDNA PrimersEosinophiliaGene ExpressionInflammationIntercellular Adhesion Molecule-1Interleukin-4Interleukin-5LungMiceMice, Inbred C57BLMice, KnockoutNF-kappa BNF-kappa B p50 SubunitOvalbuminReverse Transcriptase Polymerase Chain ReactionTh2 CellsVascular Cell Adhesion Molecule-1ConceptsAirway inflammationEosinophil-rich airway inflammationTh2 cytokine interleukin-5Adhesion molecules VCAM-1Chemokine macrophage inflammatory proteinCell adhesion molecule VCAM-1Allergic airway inflammationEosinophilic airway inflammationT cell primingPathogenesis of asthmaT helper 2T cell recruitmentInduction of eosinophiliaMacrophage inflammatory proteinCytokines interleukin-5Wild-type miceSites of inflammationNuclear factor κBAllergic asthmaAsthmatic airwaysHelper 2Cell primingInflammatory proteinMIP-1betaExtravasation of eosinophils
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 secretionTranscription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-specific Expression of the Interleukin-5 Gene*
Zhang D, Cohn L, Ray P, Bottomly K, Ray A. Transcription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-specific Expression of the Interleukin-5 Gene*. Journal Of Biological Chemistry 1997, 272: 21597-21603. PMID: 9261181, DOI: 10.1074/jbc.272.34.21597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClone CellsDNA-Binding ProteinsDown-RegulationGATA3 Transcription FactorGene Expression Regulation, DevelopmentalHeLa CellsHumansInterleukin-5Lymphocyte ActivationMiceNFATC Transcription FactorsNuclear ProteinsPromoter Regions, GeneticRNA, MessengerSpleenTh1 CellsTh2 CellsTrans-ActivatorsTranscription Factor AP-1Transcription FactorsTranscription, GeneticTranscriptional ActivationUp-RegulationConceptsGene expressionPromoter activationTranscription factor GATA-3Th2 cellsTh1 cellsGATA-3 sitesGATA-3 activityInterleukin-5 geneGATA-3GATA-3 proteinIL-5 promoterIL-5 geneTh2-specific expressionEctopic expressionMolecular basisInterleukin-5T cell receptor transgenic miceT helper 2 cellsReceptor transgenic miceTh2-type cytokinesTreatment of asthmaT helper cellsGATA-3 gene expressionDevelopment of eosinophiliaEL-4 cells