2023
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleomycinFibroblastsFibrosisHumansIdiopathic Pulmonary FibrosisInflammationLungMiceConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetLow CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity.
Li X, Guerra S, Ledford JG, Kraft M, Li H, Hastie AT, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Israel E, Jarjour NN, Levy BD, Mauger DT, Moore WC, Zein J, Kaminski N, Wenzel SE, Woodruff PG, Meyers DA, Bleecker ER. Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 438-451. PMID: 36066606, PMCID: PMC9940145, DOI: 10.1164/rccm.202206-1230oc.Peer-Reviewed Original ResearchConceptsBronchial epithelial cellsMRNA expression levelsAsthma severityT2 biomarkersAsthma susceptibilityT2 inflammationExpression levelsSevere Asthma Research ProgramSystemic corticosteroid useLower pulmonary functionEpithelial cellsAsthma-related phenotypesCorticosteroid useAsthma exacerbationsPulmonary functionAsthma developmentAsthma endotypesAsthma progressionInflammation biomarkersInflammation genesHost defenseCC16Th2 genesSeverityBiomarkers
2022
Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea.
Cortese R, Adams T, Cataldo K, Hummel J, Kaminski N, Kheirandish-Gozal L, Gozal D. Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea. European Respiratory Journal 2022, 61: 2201465. PMID: 36356973, DOI: 10.1183/13993003.01465-2022.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildHumansInflammationLeukocytes, MononuclearSingle-Cell Gene Expression AnalysisSleep Apnea, ObstructiveConceptsObstructive sleep apnoeaSleep apnoeaImpact of OSASystemic immune functionMononuclear cell compositionMolecular signaturesCell-specific markersSystemic inflammationCardiovascular dysfunctionImmune cellsImmune functionSingle-cell transcriptomic analysisPaediatric sleep apnoeaUndescribed cell typePrevalent diseaseMajor causeCellular compositionApnoeaCell compositionRNA expression datasetsDiagnostic settingCell typesCell lineagesMolecular diagnostic settingScRNA-seq
2021
Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Bui LT, Winters NI, Chung MI, Joseph C, Gutierrez AJ, Habermann AC, Adams TS, Schupp JC, Poli S, Peter LM, Taylor CJ, Blackburn JB, Richmond BW, Nicholson AG, Rassl D, Wallace WA, Rosas IO, Jenkins RG, Kaminski N, Kropski JA, Banovich NE. Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity. Nature Communications 2021, 12: 4314. PMID: 34262047, PMCID: PMC8280215, DOI: 10.1038/s41467-021-24467-0.Peer-Reviewed Original ResearchConceptsChronic lung diseaseLung diseaseImmune responseSARS-CoV-2 entry factorsSevere coronavirus disease-19SARS-CoV-2 infectionWorse COVID-19 outcomesSARS-CoV-2 entryAdaptive immune responsesCoronavirus disease-19COVID-19 outcomesInnate immune responseInflammatory gene expression programSimilar cellular distributionPoor outcomePeripheral lungViral exposureDisease-19Inflammatory microenvironmentEntry factorsLung epitheliumLung cellsViral replicationAT2 cellsBasal differencesElevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controlsPINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury
Zhang Y, Yu G, Kaminski N, Lee P. PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1118-l1125. PMID: 33851544, PMCID: PMC8285622, DOI: 10.1152/ajplung.00598.2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHyperoxiaInflammationLungLung InjuryMice, KnockoutMitochondriaProtein KinasesTriiodothyronineConceptsLung injuryWT miceThyroid hormonesBronchoalveolar lavageHyperoxia exposureBAL total cell countT3 pretreatmentAdult wild-type miceAdministration of PTULung cellular infiltratesAcute lung injuryWild-type miceNovel protective roleRespiratory failureCellular infiltrateThyroid hormone T3Total cell countHistological changesProtective effectPotential therapyProtective roleCell countCytoprotective effectsMitochondrial injuryHyperoxia
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytes
2019
Sialylation 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
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammation
2014
Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report
Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, Anstrom KJ, Bar-Joseph Z, Bitterman P, Blackburn MR, Bradford W, Brown KK, Chapman HA, Collard HR, Cosgrove GP, Deterding R, Doyle R, Flaherty KR, Garcia CK, Hagood JS, Henke CA, Herzog E, Hogaboam CM, Horowitz JC, King TE, Loyd JE, Lawson WE, Marsh CB, Noble PW, Noth I, Sheppard D, Olsson J, Ortiz LA, O’Riordan T, Oury TD, Raghu G, Roman J, Sime PJ, Sisson TH, Tschumperlin D, Violette SM, Weaver TE, Wells RG, White ES, Kaminski N, Martinez FJ, Wynn TA, Thannickal VJ, Eu JP. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 214-222. PMID: 24160862, PMCID: PMC3983890, DOI: 10.1164/rccm.201306-1141ws.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIdiopathic pulmonary fibrosisAlveolar epithelial injuryEffective medical therapyRole of inflammationTime of diagnosisPatient advocacy groupsMedian survivalMedical therapyEpithelial injuryPulmonary fibrosisPulmonary fibrosis researchIPF therapyIPF researchPreclinical modelingDrug AdministrationPatient communityU.S. FoodNHLBITranslation of discoveriesClinical researchersPatientsFibrosis researchTherapyDiseaseAberrant repair
2013
Gene expression profiles reveal molecular mechanisms involved in the progression and resolution of bleomycin-induced lung fibrosis
Cabrera S, Selman M, Lonzano-Bolaños A, Konishi K, Richards TJ, Kaminski N, Pardo A. Gene expression profiles reveal molecular mechanisms involved in the progression and resolution of bleomycin-induced lung fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2013, 304: l593-l601. PMID: 23457188, PMCID: PMC4116413, DOI: 10.1152/ajplung.00320.2012.Peer-Reviewed Original ResearchConceptsLung fibrosisFibrotic responseResolution of bleomycinTranscriptional signatureGene expression profilesGene microarray analysisC57BL/6 miceProminent inflammationSingle doseExtracellular matrix-related genesInitial progressionControl animalsTIMP-1Normal architectureExpression profilesFibrosisMatrix metalloproteinasesHydroxyproline contentBleomycinMatrix-related genesSubsequent resolutionProgressionInflammationEqual volumeMicroarray analysis
2008
Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury
Dolinay T, Wu W, Kaminski N, Ifedigbo E, Kaynar AM, Szilasi M, Watkins SC, Ryter SW, Hoetzel A, Choi AM. Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury. PLOS ONE 2008, 3: e1601. PMID: 18270588, PMCID: PMC2223071, DOI: 10.1371/journal.pone.0001601.Peer-Reviewed Original ResearchConceptsVentilator-induced lung injuryMatrix metalloproteinase-8Lung injuryInflammatory lung injuryWild-type miceMechanical ventilationProtein kinase kinase 3C57/BL6 wild-type miceLung injury parametersTerminal kinase 1C-JunLung vascular permeabilityProtein kinaseKinase 1Kinase 3Edema formationMitogen-activated protein kinase kinase 3Metalloproteinase-8Vascular permeabilityMitogen-activated protein kinase pathwayInjuryInjury parametersComprehensive gene expression profilingMiceProtein leakage
2005
Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis
Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A. Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2005, 173: 188-198. PMID: 16166619, PMCID: PMC2662988, DOI: 10.1164/rccm.200504-644oc.Peer-Reviewed Original ResearchConceptsGene expression signaturesExpression signaturesCustom oligonucleotide microarrayGene expression patternsOligonucleotide DNA microarrayStandard Affymetrix protocolGene clusterDNA microarraysExpression patternsGene expressionOligonucleotide microarraysComplementary ribonucleic acidTranscriptional signatureProbe setsCustom arrayT cell activationTissue remodelingNonspecific interstitial pneumoniaRibonucleic acidGenesMicroarrayInterstitial lung diseaseHypersensitivity pneumonitisPathogenic mechanismsExpression
2004
Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus
MANDEL M, GUREVICH M, PAUZNER R, KAMINSKI N, ACHIRON A. Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus. Clinical & Experimental Immunology 2004, 138: 164-170. PMID: 15373920, PMCID: PMC1809188, DOI: 10.1111/j.1365-2249.2004.02587.x.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusPeripheral blood mononuclear cellsMultiple sclerosisHealthy subjectsAutoimmune signatureSLE patientsLupus erythematosusAutoimmune diseasesRelapsing-remitting MS patientsBlood mononuclear cellsMatrix metalloproteinase pathwayAdditional blood samplesDisease-specific signaturesDisease-associated signaturesTIMP1 gene expressionGene expression signaturesMS patientsMononuclear cellsSpecific therapyGene expression findingsMetalloproteinase pathwayNuclear autoantibodiesBlood samplesMMP activityPatientsBlood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity
Achiron A, Gurevich M, Friedman N, Kaminski N, Mandel M. Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity. Annals Of Neurology 2004, 55: 410-417. PMID: 14991819, DOI: 10.1002/ana.20008.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMultiple sclerosisMS patientsTranscriptional signatureCentral nervous system diseaseBlood transcriptional signaturesBlood mononuclear cellsNervous system diseasesT cell activationAcute relapseDisease activityImmunomodulatory treatmentMS pathogenesisActive demyelinationMononuclear cellsUnpredictable courseImmune surveillanceCellular recruitmentSystem diseasesTherapeutic strategiesDisease processDisease pathogenesisUnique gene expressionSclerosisPatients
2003
Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema
Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick A, Sheppard D. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 2003, 422: 169-173. PMID: 12634787, DOI: 10.1038/nature01413.Peer-Reviewed Original ResearchConceptsTGF-β activationLungs of miceActive TGF-β1Pulmonary gene expressionHeterodimeric cell-surface proteinsTransgenic expressionPulmonary emphysemaMMP12 expressionTGF-β1Functional alterationsΒ6 integrinIntegrin αvβ6Latent TGFMarked inductionEmphysemaGrowth factorMacrophage metalloelastaseCell surface proteinsActivation pathwayMiceTGFActivationCell growthIntegrinsExpression
2002
Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis
Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Medicine 2002, 8: 500-508. PMID: 11984595, DOI: 10.1038/nm0502-500.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAutopsyChronic DiseaseEncephalomyelitis, Autoimmune, ExperimentalFemaleGranulocyte Colony-Stimulating FactorHumansInflammationInterferon-gammaInterleukin-17Interleukin-6MiceMice, Inbred C57BLMultiple SclerosisOligonucleotide Array Sequence AnalysisReceptors, FcReproducibility of ResultsTranscription, GeneticConceptsExperimental autoimmune encephalomyelitisMultiple sclerosis lesionsMS lesionsAutoimmune encephalomyelitisSclerosis lesionsGranulocyte colony-stimulating factorCommon γ chainColony-stimulating factorGene microarray analysisAcute phaseInflammatory cytokinesInterleukin-6Chronic diseasesLesionsNew targetsEncephalomyelitisTherapyDownstream pathwaysMicroarray analysisΓ-chainMicroarray studiesInflammationChronicCytokinesInterferon
2000
Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis
Kaminski N, Allard J, Pittet J, Zuo F, Griffiths M, Morris D, Huang X, Sheppard D, Heller R. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 1778-1783. PMID: 10677534, PMCID: PMC26512, DOI: 10.1073/pnas.97.4.1778.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisLung inflammationBleomycin administrationSusceptible miceMultiple time pointsFibrotic responseFibrosisFibrotic diseasesInflammationMore effective strategiesGene expressionTime pointsMiceBeta6 subunitMolecular mechanismsSequential inductionGene expression patternsExpression patternsNull mutationResponseEffective strategyLungExpressionBleomycinGene expression programs