2024
A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Everman J, Sajuthi S, Liegeois M, Jackson N, Collet E, Peters M, Chioccioli M, Moore C, Patel B, Dyjack N, Powell R, Rios C, Montgomery M, Eng C, Elhawary J, Mak A, Hu D, Huntsman S, Salazar S, Feriani L, Fairbanks-Mahnke A, Zinnen G, Michel C, Gomez J, Zhang X, Medina V, Chu H, Cicuta P, Gordon E, Zeitlin P, Ortega V, Reisdorph N, Dunican E, Tang M, Elicker B, Henry T, Bleecker E, Castro M, Erzurum S, Israel E, Levy B, Mauger D, Meyers D, Sumino K, Gierada D, Hastie A, Moore W, Denlinger L, Jarjour N, Schiebler M, Wenzel S, Woodruff P, Rodriguez-Santana J, Pearson C, Burchard E, Fahy J, Seibold M. A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma. Nature Communications 2024, 15: 3900. PMID: 38724552, PMCID: PMC11082194, DOI: 10.1038/s41467-024-48034-5.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsIntelectin-1Mucus pluggingGene expressionAirways of severe asthmaticsEpithelial cellsHuman airway epithelial cellsAirway epithelial brushingsMucus secretory cellsT2-high asthmaFormation of mucus plugsAssociated with protectionC-terminusGenetic variantsAirway mucus pluggingMolecular roleSecretory cellsSecreted componentsEpithelial brushingsT2-lowIL-13Mucus obstructionTarget pathwaysSevere asthmaticsClinical significanceLytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells
Zamora P, Reidy T, Armbruster C, Sun M, Van Tyne D, Turner P, Koff J, Bomberger J. Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells. PLOS Biology 2024, 22: e3002566. PMID: 38652717, PMCID: PMC11037538, DOI: 10.1371/journal.pbio.3002566.Peer-Reviewed Original ResearchConceptsLytic phagesLytic bacteriophagesPhage therapyAirway epithelial cellsPseudomonas aeruginosa phagesEpithelial cellsMultidrug resistanceAirway epitheliumCystic fibrosisProinflammatory cytokinesHuman respiratory epithelial cellsPhage exposurePhage familiesMammalian cell responsesHuman airway epithelial cellsInternalized phageTreat multidrug-resistantPhageBacterial isolatesTranscriptional profilesRespiratory epithelial cellsHuman hostChronic respiratory disordersBacterial biofilmsBacteriophageFibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung
Justet A, Pineda H, Adams T, Balayev A, Mitash N, Ishizuka M, Kim H, Khoury J, Cala-García J, Flint J, Schupp J, Ahangari F, Yan X, Rosas I, Kaminski N, Königshoff M. Fibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung. Revue Des Maladies Respiratoires 2024, 41: 218. DOI: 10.1016/j.rmr.2024.01.074.Peer-Reviewed Original ResearchCellular repertoireCell typesSingle cell platformsSequence readsCDNA libraryIllumina platformHuman genomeNucleus transcriptomicsCellular diversityIPF lungsPulmonary fibrosisEMT markersAirway epithelial cellsBasaloid cellsCellular populationsEpithelial cellsFibrotic fibroblastsCell platformLung slicesLung cell populationsHuman precision-cut lung slicesCell populationsSenescence markersCellsBasal markersIdentification of abnormal airway niches in the fibrotic lung using spatial transcriptomics
Justet A, Ravaglia C, Zhao A, Adams N, Agshin B, Kaminski N, Tomasseti S, Poletti V. Identification of abnormal airway niches in the fibrotic lung using spatial transcriptomics. Revue Des Maladies Respiratoires 2024, 41: 215. DOI: 10.1016/j.rmr.2024.01.068.Peer-Reviewed Original ResearchVascular endothelial cellsIPF patientsIPF lungsEpithelial cellsLung tissueEndothelial cellsCOVID patientsAirway epithelial cellsAbnormal cell populationsAlveolar epithelial cellsProgression to fibrosisLong COVIDBasaloid cellsControl patientsImmune cellsGene panelFFPE slidesFibrotic lungsProximal airwaysPatientsDistal lungLungBasal cellsCell populationsLong COVID patients
2023
Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis
Bahudhanapati H, Tan J, Apel R, Seeliger B, Schupp J, Li X, Sullivan D, Sembrat J, Rojas M, Tabib T, Valenzi E, Lafyatis R, Mitash N, Pineda R, Jawale C, Peroumal D, Biswas P, Tedrow J, Adams T, Kaminski N, Wuyts W, McDyer J, Gibson K, Alder J, Königshoff M, Zhang Y, Nouraie M, Prasse A, Kass D. Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis. European Respiratory Journal 2023, 63: 2300088. PMID: 37918852, DOI: 10.1183/13993003.00088-2023.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway epithelial cellsBronchoalveolar lavagePulmonary fibrosisEpithelial cellsCollagen synthesisPathogenesis of IPFCohort of patientsIPF lung fibroblastsEffects of chemokinesAir-liquid interface culturesExpression of CXCL6Collagen I levelsIPF mortalityIPF patientsChemokine levelsIPF fibroblastsPoor survivalDistal lungI levelsWhole lungAnimal modelsEctopic localisationPatientsSingle-cell RNA sequencing194 Investigating the role of bromodomain-containing 8 isoforms in the innate immune response of human airway epithelial cells
Browne J, Bruscia E, Garrison A, Harris A, Egan M. 194 Investigating the role of bromodomain-containing 8 isoforms in the innate immune response of human airway epithelial cells. Journal Of Cystic Fibrosis 2023, 22: s101. DOI: 10.1016/s1569-1993(23)01124-4.Peer-Reviewed Original ResearchHuman airway epithelial cellsAirway epithelial cellsInnate immune responseImmune responseEpithelial cellsSpatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia
Castaneda D, Jangra S, Yurieva M, Martinek J, Callender M, Coxe M, Choi A, Diego J, Lin J, Wu T, Marches F, Chaussabel D, Yu P, Salner A, Aucello G, Koff J, Hudson B, Church S, Gorman K, Anguiano E, García-Sastre A, Williams A, Schotsaert M, Palucka K. Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia. IScience 2023, 26: 107374. PMID: 37520727, PMCID: PMC10374611, DOI: 10.1016/j.isci.2023.107374.Peer-Reviewed Original ResearchHuman air-liquid interface culturesAir-liquid interface culturesNucleoprotein expressionAirway epithelial cellsSARS-CoV-2 variant infectionResponse to virusesUnmet medical needCSF3 expressionInterface culturesImmune responseEpithelial cellsDay 4Severe diseaseVariant infectionBasal cellsTranscriptional signatureSARS-CoV-2InfectionApical cellsEarly responseMedical needSARS-CoV-2 virusEpitheliaVirusPost-infectionPharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2022
Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma
Mank M, Reed L, Fastiggi V, Peña-García P, Hoyt L, Van Der Vliet K, Ather J, Poynter M. Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma. Journal Of Allergy And Clinical Immunology Global 2022, 1: 282-298. PMID: 36466740, PMCID: PMC9718535, DOI: 10.1016/j.jacig.2022.08.001.Peer-Reviewed Original ResearchKetone ester supplementationMethacholine hyperresponsivenessAllergic asthmaAirway epithelial cellsKetogenic dietDose-dependent mannerKetone bodiesMouse modelElicit anti-inflammatory activityAllergic asthmatic individualsBronchial smooth muscle cellsChronic allergic asthmaHuman airway epithelial cellsEpithelial cellsProinflammatory cytokine secretionIL-8 secretionAnti-inflammatory activityBHB concentrationsSmooth muscle cellsKetone body precursorsRange of mildHDM sensitizationObese asthmaCell typesCorticosteroid treatment
2021
Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells
Paranjapye A, NandyMazumdar M, Browne JA, Leir SH, Harris A. Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells. Journal Of Biological Chemistry 2021, 297: 100932. PMID: 34217701, PMCID: PMC8353497, DOI: 10.1016/j.jbc.2021.100932.Peer-Reviewed Original ResearchConceptsKrüppel-like factor 5Lung epithelial cell lineEpithelial cell lineHistone modification H3K27acEpithelial cell identityDirect gene targetsSiRNA-mediated depletionHuman airway epithelial cellsCCAAT enhancer-binding protein betaEnhancer-binding protein betaCell linesSecretion of cytokinesAirway epithelial cellsHuman lung diseasesInnate immune responseHuman airway epitheliumPseudomonas aeruginosa lipopolysaccharideFactor 5Cell identityCalu-3 cellsChIP-seqTranscription factorsRNA-seqGene targetsIL-1β
2020
Flavor-solvent reaction products in electronic cigarette liquids activate respiratory irritant receptors and elicit cytotoxic metabolic responses in airway epithelial cell
Jordt S, Caceres A, Erythropel H, Zimmerman J, Dewinter T, Jabba S. Flavor-solvent reaction products in electronic cigarette liquids activate respiratory irritant receptors and elicit cytotoxic metabolic responses in airway epithelial cell. 2020, 4384. DOI: 10.1183/13993003.congress-2020.4384.Peer-Reviewed Original ResearchAirway epithelial cellsIrritant receptorsElectronic cigarette liquidsEpithelial cellsMetabolic responseSARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
Ziegler C, Allon S, Nyquist S, Mbano I, Miao V, Tzouanas C, Cao Y, Yousif A, Bals J, Hauser B, Feldman J, Muus C, Wadsworth M, Kazer S, Hughes T, Doran B, Gatter G, Vukovic M, Taliaferro F, Mead B, Guo Z, Wang J, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre J, Taylor C, Lin B, Waghray A, Mitsialis V, Dwyer D, Buchheit K, Boyce J, Barrett N, Laidlaw T, Carroll S, Colonna L, Tkachev V, Peterson C, Yu A, Zheng H, Gideon H, Winchell C, Lin P, Bingle C, Snapper S, Kropski J, Theis F, Schiller H, Zaragosi L, Barbry P, Leslie A, Kiem H, Flynn J, Fortune S, Berger B, Finberg R, Kean L, Garber M, Schmidt A, Lingwood D, Shalek A, Ordovas-Montanes J, Network H, Banovich N, Barbry P, Brazma A, Desai T, Duong T, Eickelberg O, Falk C, Farzan M, Glass I, Haniffa M, Horvath P, Hung D, Kaminski N, Krasnow M, Kropski J, Kuhnemund M, Lafyatis R, Lee H, Leroy S, Linnarson S, Lundeberg J, Meyer K, Misharin A, Nawijn M, Nikolic M, Ordovas-Montanes J, Pe’er D, Powell J, Quake S, Rajagopal J, Tata P, Rawlins E, Regev A, Reyfman P, Rojas M, Rosen O, Saeb-Parsy K, Samakovlis C, Schiller H, Schultze J, Seibold M, Shalek A, Shepherd D, Spence J, Spira A, Sun X, Teichmann S, Theis F, Tsankov A, van den Berge M, von Papen M, Whitsett J, Xavier R, Xu Y, Zaragosi L, Zhang K. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020, 181: 1016-1035.e19. PMID: 32413319, PMCID: PMC7252096, DOI: 10.1016/j.cell.2020.04.035.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlveolar Epithelial CellsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell LineCells, CulturedChildCoronavirus InfectionsCOVID-19EnterocytesGoblet CellsHIV InfectionsHumansInfluenza, HumanInterferon Type ILungMacaca mulattaMiceMycobacterium tuberculosisNasal MucosaPandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptors, VirusSARS-CoV-2Serine EndopeptidasesSingle-Cell AnalysisTuberculosisUp-RegulationConceptsSARS-CoV-2Interferon-stimulated genesAirway epithelial cellsCell subsetsSingle-cell RNA sequencing datasetsRNA sequencing datasetsSARS-CoV-2 receptor ACE2Human interferon-stimulated genesTransmembrane serine protease 2Human airway epithelial cellsEpithelial cellsSevere acute respiratory syndrome coronavirus clade 2SARS-CoV-2 spike proteinType II pneumocytesSerine protease 2Clade 2Putative targetsNon-human primatesSpecific cell subsetsCo-expressing cellsDisease COVID-19ACE2 expressionLung injuryLung type II pneumocytesAbsorptive enterocytes
2019
Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells
Chioccioli M, Feriani L, Kotar J, Bratcher PE, Cicuta P. Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells. Nature Communications 2019, 10: 1763. PMID: 30992452, PMCID: PMC6467870, DOI: 10.1038/s41467-019-09798-3.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial cellsCystic fibrosis respiratory epithelial cellsAirway epithelial cellsRespiratory epithelial cellsCiliary beat frequencyCiliary beatingRespiratory disordersRespiratory diseaseClinical observationsCystic fibrosisDrug efficacyPilot studyDrug testingEfficient drugsDrugsIndividual donorsEfficacyDrug screeningBeat dynamicsCellsSame genotypeFibrosisDonorsDiseaseSialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation
Zhou X, Kinlough CL, Hughey RP, Jin M, Inoue H, Etling E, Modena BD, Kaminski N, Bleecker ER, Meyers DA, Jarjour NN, Trudeau JB, Holguin F, Ray A, Wenzel SE. Sialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation. JCI Insight 2019, 4 PMID: 30730306, PMCID: PMC6483602, DOI: 10.1172/jci.insight.122475.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial dysfunctionPrimary human airway epithelial cellsAirway epithelial cell differentiationT2-high asthmaType 2 inflammationAirway epithelial cellsGoblet cell differentiationEpithelial cell proliferationAirway specimensT2 biomarkersAsthmatic patientsSputum supernatantsT2 inflammationIL-13Cell differentiationAsthmaEpithelial cell differentiationSpecific mucinsEpithelial cell fateΒ-galactoside αEpithelial glycoproteinEpithelial cellsPotential targetEpithelial differentiation
2018
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Mihaylova VT, Kong Y, Fedorova O, Sharma L, Dela Cruz CS, Pyle AM, Iwasaki A, Foxman EF. Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. Cell Reports 2018, 24: 3000-3007.e3. PMID: 30208323, PMCID: PMC6190718, DOI: 10.1016/j.celrep.2018.08.033.Peer-Reviewed Original ResearchConceptsRIG-I stimulationAntiviral responseRhinovirus infectionBronchial airway epithelial cellsAcute respiratory infectionsEpithelial cellsRobust antiviral responseAirway epithelial cellsPrimary human nasalAirway damageRespiratory infectionsAirway microenvironmentAsthma attacksNasal mucosaLeading causeNrf2 knockdownNasal cellsNrf2 activationHuman nasalEpithelial defenseHost defenseBronchial cellsInfectionOxidative stressRhinovirusA role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
McDonough JE, Martens DS, Tanabe N, Ahangari F, Verleden SE, Maes K, Verleden GM, Kaminski N, Hogg JC, Nawrot TS, Wuyts WA, Vanaudenaerde BM. A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis. Respiratory Research 2018, 19: 132. PMID: 29986708, PMCID: PMC6038197, DOI: 10.1186/s12931-018-0838-4.Peer-Reviewed Original ResearchConceptsIPF lungsDisease severityChromosomal damagePulmonary fibrosisTelomere lengthBackgroundIdiopathic pulmonary fibrosisRegional disease severityStructural disease severityIdiopathic pulmonary fibrosisFatal lung diseaseAirway epithelial cellsMultivariate linear mixed-effects modelDonor lungsFibroblastic fociLung diseaseFibrotic markersTransplant surgeryPathological changesSevere diseaseLungLinear mixed-effects modelsQuantitative histologyMixed-effects modelsExtracellular matrixSeverityA transcription factor network represses CFTR gene expression in airway epithelial cells.
Mutolo MJ, Leir SH, Fossum SL, Browne JA, Harris A. A transcription factor network represses CFTR gene expression in airway epithelial cells. Biochemical Journal 2018, 475: 1323-1334. PMID: 29572268, PMCID: PMC6380350, DOI: 10.1042/bcj20180044.Peer-Reviewed Original ResearchConceptsCystic fibrosisTranscription factorsAirway epitheliumEpithelial cellsCalu-3 lung epithelial cellsPrimary human bronchial epithelial cellsAirway epithelium resultsKrüppel-like factor 5Novel therapeutic targetAirway epithelial cellsEts homologous factorHuman bronchial epithelial cellsTranscription factor networkBronchial epithelial cellsLung epithelial cellsTissue-specific enhancersCystic fibrosis transmembrane conductance regulator (CFTR) geneCFTR gene expressionAirway expressionTransmembrane conductance regulator geneLung diseaseCFTR mRNA levelsPancreatic ductTherapeutic targetCF morbidity
2016
Early local immune defences in the respiratory tract
Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nature Reviews Immunology 2016, 17: 7-20. PMID: 27890913, PMCID: PMC5480291, DOI: 10.1038/nri.2016.117.Peer-Reviewed Original ResearchConceptsRespiratory tractImmune responseDendritic cellsType 2 immune responsesType 1 immune responsePlasmacytoid dendritic cellsEpithelial cellsTissue-resident lymphocytesLower respiratory tractType of infectionUpper respiratory tractAirway epithelial cellsLocal immune defensePattern recognition receptorsAntimicrobial host defenseLymphoid cell typesCell typesRespiratory infectionsEffector cellsSecrete cytokinesAllergen resultsInnate sensorsMast cellsAirway cellsPathological inflammation
2015
Anti-Inflammatory Effects of Levalbuterol-Induced 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Airway Epithelial Cells
Randall MJ, Kostin SF, Burgess EJ, Hoyt LR, Ather JL, Lundblad LK, Poynter ME. Anti-Inflammatory Effects of Levalbuterol-Induced 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Airway Epithelial Cells. Frontiers In Endocrinology 2015, 5: 236. PMID: 25628603, PMCID: PMC4290686, DOI: 10.3389/fendo.2014.00236.Peer-Reviewed Original ResearchAirway epithelial cellsPro-inflammatory cytokine productionNF-κB activationAsthmatic subjectsCytokine productionRacemic albuterolEpithelial cellsEpithelial NF-κB activationAnti-inflammatory effectsNF-κB transcriptional activityTumor necrosis factorType 1 activityNF-κB activityAirway inflammationAllergic asthmaEndogenous glucocorticoidsLung functionCombination therapyNecrosis factorCorticosteroidsLuc activityAugments expressionAlbuterolMouse modelNF-κBTemperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells
Foxman EF, Storer JA, Fitzgerald ME, Wasik BR, Hou L, Zhao H, Turner PE, Pyle AM, Iwasaki A. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 827-832. PMID: 25561542, PMCID: PMC4311828, DOI: 10.1073/pnas.1411030112.Peer-Reviewed Original ResearchConceptsAirway cellsCommon cold virusViral replicationIFN inductionRecombinant type I IFNMouse airway epithelial cellsCold virusAirway epithelial cellsInduction of ISGsType I IFNPrimary airway cellsCore body temperatureType IAntiviral defense responseLike receptorsI IFNNasal cavityMAVS proteinHuman rhinovirusSustained increaseInnate defensePoly IGenetic deficiencyRobust inductionRhinovirus
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