2024
Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantSingle-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 1252-1266. PMID: 38924775, PMCID: PMC11568434, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsFibrotic 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 markers
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, Hernandez 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 sequencingVascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling.
Yanagihara T, Tsubouchi K, Zhou Q, Chong M, Otsubo K, Isshiki T, Schupp J, Sato S, Scallan C, Upagupta C, Revill S, Ayoub A, Chong S, Dvorkin-Gheva A, Kaminski N, Tikkanen J, Keshavjee S, Paré G, Guignabert C, Ask K, Kolb M. Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 1498-1514. PMID: 36917778, DOI: 10.1164/rccm.202109-2174oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVascular smooth muscle cellsAdvanced idiopathic pulmonary fibrosisPulmonary hypertensionFibrotic lungsVascular remodelingEndothelial cellsPulmonary fibrosisLung diseaseLung fibrosisDevelopment of PHConcomitant pulmonary hypertensionProgressive lung scarringPulmonary vascular remodelingFibrotic lung diseaseProgression of fibrosisActivation of VSMCsActive TGF-β1Fatal lung diseaseSmooth muscle cellsWhole-exome sequencingLung scarringEndothelial dysfunctionPoor prognosisFibrogenic effectsmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouse
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacyAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Jaeger B, Schupp JC, Plappert L, Terwolbeck O, Artysh N, Kayser G, Engelhard P, Adams TS, Zweigerdt R, Kempf H, Lienenklaus S, Garrels W, Nazarenko I, Jonigk D, Wygrecka M, Klatt D, Schambach A, Kaminski N, Prasse A. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nature Communications 2022, 13: 5637. PMID: 36163190, PMCID: PMC9513076, DOI: 10.1038/s41467-022-33193-0.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsPulmonary fibrosisNovel mouse xenograft modelEffect of saracatinibBasal cellsLimited treatment optionsMouse xenograft modelLung developmental processesConnectivity Map analysisExtracellular matrix depositionIPF lungsBronchial brushSevere fibrosisTreatment optionsBronchial brushingsNRG miceHealthy volunteersXenograft modelCyst-like structuresProfibrotic changesAlveolar compartmentFatal diseaseFibrosisPotent Src inhibitorFK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis
Preisendörfer S, Ishikawa Y, Hennen E, Winklmeier S, Schupp JC, Knüppel L, Fernandez IE, Binzenhöfer L, Flatley A, Juan-Guardela BM, Ruppert C, Guenther A, Frankenberger M, Hatz RA, Kneidinger N, Behr J, Feederle R, Schepers A, Hilgendorff A, Kaminski N, Meinl E, Bächinger HP, Eickelberg O, Staab-Weijnitz CA. FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis. Cells 2022, 11: 1341. PMID: 35456020, PMCID: PMC9027113, DOI: 10.3390/cells11081341.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPlasma cellsPulmonary fibrosisIgG antibodiesFatal chronic lung diseaseCell linesAntibody-producing plasma cellsChronic lung diseaseAdaptive immune responsesHybridoma cell linesAlveolar epithelial cell lineCell-specific antibodiesCell deathAntibody-producing hybridoma cellsAutoimmune featuresX-box-binding protein 1IPF lungsLung diseaseEpithelial cell lineImmune responseLymphatic tissueB cellsStress-mediated cell deathAntibody secretionER stress-mediated cell deathBAL Transcriptomes Characterize Idiopathic Pulmonary Fibrosis Endotypes With Prognostic Impact
De Sadeleer LJ, Verleden SE, Schupp JC, McDonough JE, Goos T, Yserbyt J, Bargagli E, Rottoli P, Kaminski N, Prasse A, Wuyts WA. BAL Transcriptomes Characterize Idiopathic Pulmonary Fibrosis Endotypes With Prognostic Impact. CHEST Journal 2022, 161: 1576-1588. PMID: 35063449, PMCID: PMC9424328, DOI: 10.1016/j.chest.2021.12.668.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF samplesIndependent validation cohortAvailable gene expression datasetsClinical characteristicsPrognostic impactWorse survivalPathophysiologic mechanismsPulmonary fibrosisClinical evolutionClinical variablesValidation cohortEnrichment analysisBAL samplesSurvival-associated genesBlood samplesEndotypesStudy designControl participantsMitochondrial dysfunctionPatientsFibrosisSurvivalTranscription factorsNumeric trendsLung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.
De Sadeleer LJ, McDonough JE, Schupp JC, Yan X, Vanstapel A, Van Herck A, Everaerts S, Geudens V, Sacreas A, Goos T, Aelbrecht C, Nawrot TS, Martens DS, Schols D, Claes S, Verschakelen JA, Verbeken EK, Ackermann M, Decottignies A, Mahieu M, Hackett TL, Hogg JC, Vanaudenaerde BM, Verleden SE, Kaminski N, Wuyts WA. Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2022, 205: 60-74. PMID: 34724391, PMCID: PMC8865586, DOI: 10.1164/rccm.202103-0569oc.Peer-Reviewed Original ResearchConceptsFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisHypersensitivity pneumonitisLung zonesMolecular traitsUnused donor lungsInterstitial lung diseaseLocal disease extentProgression of fibrosisSevere fibrosis groupGene co-expression network analysisCo-expression network analysisExplant lungsDonor lungsLung involvementEndothelial functionLung findingsDisease extentPulmonary fibrosisLung diseaseFibrosis groupLung microenvironmentClinical behaviorDisease progressionBAL samples
2021
S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis
Behr J, Günther A, Bonella F, Dinkel J, Fink L, Geiser T, Geissler K, Gläser S, Handzhiev S, Jonigk D, Koschel D, Kreuter M, Leuschner G, Markart P, Prasse A, Schönfeld N, Schupp J, Sitter H, Müller-Quernheim J, Costabel U. S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis. Respiration 2021, 100: 238-271. PMID: 33486500, DOI: 10.1159/000512315.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisDiagnosis of IPFInternational IPF guidelinesSurgical lung biopsyDiagnosis of exclusionTransbronchial lung cryobiopsyInterstitial lung diseaseIPF patientsTypical clinical contextLung biopsyLung cryobiopsyBronchoalveolar lavageSerologic testingBronchoscopic diagnosisLung diseaseDiagnostic workupIPF guidelinesMultidisciplinary discussionStandardized questionnaireFatal diseaseUpdate 2018DiagnosisClinical contextGolden standard
2020
Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis
Tsukui T, Sun KH, Wetter JB, Wilson-Kanamori JR, Hazelwood LA, Henderson NC, Adams TS, Schupp JC, Poli SD, Rosas IO, Kaminski N, Matthay MA, Wolters PJ, Sheppard D. Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis. Nature Communications 2020, 11: 1920. PMID: 32317643, PMCID: PMC7174390, DOI: 10.1038/s41467-020-15647-5.Peer-Reviewed Original ResearchConceptsCollagen-producing cellsSitu hybridization showDisease-relevant phenotypesCell atlasDistinct localizationExpression of CTHRC1Fibrotic lungsDifferent compartmentsPulmonary fibrosisDistinct anatomical localizationCellsCTHRC1Murine lungFibroblastsIdiopathic pulmonary fibrosisAdoptive transfer experimentsLocalizationSubpopulationsComplex architectureTransfer experimentsFibroblastic fociPathologic fibrosisPathologic scarringScleroderma patientsSimilar heterogeneityS2K-Leitlinie zur Diagnostik der idiopathischen Lungenfibrose
Behr J, Günther A, Bonella F, Dinkel J, Fink L, Geiser T, Geißler K, Gläser S, Handzhhiev S, Jonigk D, Koschel D, Kreuter M, Leuschner G, Markart P, Prasse A, Schönfeld N, Schupp J, Sitter H, Müller-Quernheim J, Costabel U. S2K-Leitlinie zur Diagnostik der idiopathischen Lungenfibrose. Pneumologie 2020, 74: 263-293. PMID: 32227328, DOI: 10.1055/a-1120-3531.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIdiopathic pulmonary fibrosisIPF patientsDiagnosis of IPFInternational IPF guidelinesSurgical lung biopsyDiagnosis of exclusionTransbronchial lung cryobiopsyInterstitial lung diseaseTypical clinical settingLung biopsyLung cryobiopsyBronchoalveolar lavagePulmonary fibrosisSerologic testingBronchoscopic diagnosisLung diseaseIPF guidelinesAntifibrotic drugsMultidisciplinary discussionFatal diseaseUpdate 2018Standardised questionnaireClinical settingPatientsDiagnosis
2019
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis
Prasse A, Binder H, Schupp JC, Kayser G, Bargagli E, Jaeger B, Hess M, Rittinghausen S, Vuga L, Lynn H, Violette S, Jung B, Quast K, Vanaudenaerde B, Xu Y, Hohlfeld JM, Krug N, Herazo-Maya JD, Rottoli P, Wuyts WA, Kaminski N. BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 622-630. PMID: 30141961, PMCID: PMC6396865, DOI: 10.1164/rccm.201712-2551oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseaseBAL cellsBasal cellsPulmonary fibrosisControl subjectsCell gene expressionIndependent IPF cohortsNine-gene signatureIPF cohortDerivation cohortClinical parametersRetrospective studyUnivariate analysisUnpredictable courseCell involvementDiscovery cohortGene expressionHealthy volunteersCox modelStage IIIFatal disease
2016
Usefulness of Cyclophosphamide Pulse Therapy in Interstitial Lung Diseases
Schupp J, Köhler T, Müller-Quernheim J. Usefulness of Cyclophosphamide Pulse Therapy in Interstitial Lung Diseases. Respiration 2016, 91: 296-301. PMID: 27082957, DOI: 10.1159/000445031.Peer-Reviewed Original ResearchConceptsNon-specific interstitial pneumoniaInterstitial lung diseaseLymphocytic interstitial pneumoniaCyclophosphamide pulse therapyLung functionPulse therapyInterstitial pneumoniaLung diseaseRheumatoid arthritis-associated interstitial lung diseaseIdiopathic non-specific interstitial pneumoniaFibrotic interstitial lung diseaseProgressive lung function declineBetter survival outcomesLung function declineIdiopathic pulmonary fibrosisBronchoalveolar lavage cytologyGroup of disordersILD patientsMost patientsSystemic sclerosisTotal cohortFunction declineLavage cytologyPulmonary fibrosisCyclophosphamide treatment
2015
Macrophage Activation in Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Schupp J, Binder H, Jäger B, Cillis G, Zissel G, Müller-Quernheim J, Prasse A. Macrophage Activation in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. PLOS ONE 2015, 10: e0116775. PMID: 25590613, PMCID: PMC4295887, DOI: 10.1371/journal.pone.0116775.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAcute exacerbationBAL cellsMacrophage activationPulmonary fibrosisIL-8M2 cytokinesAE of IPFBAL differential cell countsFuture acute exacerbationsM2 macrophage activationCytokine production levelsDifferential cell countsHigher baseline levelsPatients wSerial lavagesBAL neutrophilsCytokine profileNeutrophil countStable patientsDisease accelerationCCL18 levelsInitial diagnosisIL-1raIL-1β
2013
Lung Collagens Perpetuate Pulmonary Fibrosis via CD204 and M2 Macrophage Activation
Stahl M, Schupp J, Jäger B, Schmid M, Zissel G, Müller-Quernheim J, Prasse A. Lung Collagens Perpetuate Pulmonary Fibrosis via CD204 and M2 Macrophage Activation. PLOS ONE 2013, 8: e81382. PMID: 24278429, PMCID: PMC3835428, DOI: 10.1371/journal.pone.0081382.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisAlveolar macrophagesCollagen type IHealthy donorsInterleukin-1 receptor antagonistType IM2 macrophage activationExpression of CCL2Lower respiratory tractIL-1ra productionAbundant collagen productionInnate immune responsePhospho-Akt expressionType I effectsExpression of CD204Collagen breakdown productsBronchoalveolar lavageReceptor antagonistCD204 expressionRespiratory tractLung collagenImmune responseM2 typeMacrophage activation