2024
The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study
Heigl T, Kaes J, Aelbrecht C, Serré J, Yamada Y, Geudens V, Van Herck A, Vanstapel A, Sacreas A, Ordies S, Frick A, Gimenez B, Van Slambrouck J, Beeckmans H, Oztürk N, Orlitova M, Vaneylen A, Claes S, Schols D, Velde G, Schupp J, Kaminski N, Boesch M, Korf H, van der Merwe S, Dupont L, Vanoirbeek J, Godinas L, Van Raemdonck D, Janssens W, Gayan-Ramirez G, Ceulemans L, McDonough J, Verbeken E, Vos R, Vanaudenaerde B. The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study. Frontiers In Immunology 2024, 15: 1369536. PMID: 38736881, PMCID: PMC11084670, DOI: 10.3389/fimmu.2024.1369536.Peer-Reviewed Original ResearchConceptsChronic lung allograft dysfunctionChronic rejectionLung transplantationSingle cell RNASingle cell RNA profilingOrthotopic left lung transplantationComplications post-transplantationLung allograft dysfunctionMouse lung transplantationLeft lung transplantationLung transplantation studiesAllograft dysfunctionPleural infiltrationPost-transplantationBronchiolitis obliteransInnate inflammationChronic complicationsPrimary onsetEndothelial destructionTransplantationDay 7Immunological perspectiveArterial responseTransplantation studiesLung
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 efficacyRecruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetAirway 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 inhibitorCINS: Cell Interaction Network inference from Single cell expression data
Yuan Y, Cosme C, Adams TS, Schupp J, Sakamoto K, Xylourgidis N, Ruffalo M, Li J, Kaminski N, Bar-Joseph Z. CINS: Cell Interaction Network inference from Single cell expression data. PLOS Computational Biology 2022, 18: e1010468. PMID: 36095011, PMCID: PMC9499239, DOI: 10.1371/journal.pcbi.1010468.Peer-Reviewed Original ResearchConceptsCell type interactionsSingle-cell expression dataSingle-cell RNA-seq dataRNA-seq dataScRNA-seq experimentsCell-cell interactionsExpression dataCell typesMouse datasetsNetwork inferenceCell interactionsInteraction predictionNetwork analysisInference pipelineGenesCINSProteinInteractionBayesian network analysisCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2020
Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome
Morrone C, Smirnova NF, Jeridi A, Kneidinger N, Hollauer C, Schupp JC, Kaminski N, Jenne D, Eickelberg O, Yildirim AÖ. Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome. European Respiratory Journal 2020, 57: 2001416. PMID: 33303550, DOI: 10.1183/13993003.01416-2020.Peer-Reviewed Original ResearchConceptsBronchoalveolar lavage fluidCathepsin B activityHealthy donorsLung tissueCollagen depositionB activityCathepsin BBronchiolitis obliterans syndromeProgression of BOSFluorescence resonance energy transfer-based assayPromising therapeutic targetGrowth factor-β1Cathepsin B levelsSubsequent collagen depositionBOS pathogenesisBOS patientsBOS progressionLTx patientsLymphocytic bronchiolitisObliterans syndromeLung transplantationPeribronchial fibrosisPulmonary dysfunctionLung functionMajor complicationsCollagen-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 heterogeneityPlatform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing
Greaney AM, Adams TS, Raredon M, Gubbins E, Schupp JC, Engler AJ, Ghaedi M, Yuan Y, Kaminski N, Niklason LE. Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing. Cell Reports 2020, 30: 4250-4265.e6. PMID: 32209482, PMCID: PMC7175071, DOI: 10.1016/j.celrep.2020.03.004.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingBasal marker expressionBasal cellsChronic pulmonary diseaseRat tracheal epitheliumPulmonary diseaseRNA sequencingCell-based therapiesRat tracheaAir-liquid interfaceTissue graftMarker expressionTracheal epitheliumRegenerative outcomesTracheaEpithelial progenitorsDifferential outcomesEpitheliumOutcomesWhole organPopulation level
2019
Single-cell connectomic analysis of adult mammalian lungs
Raredon MSB, Adams TS, Suhail Y, Schupp JC, Poli S, Neumark N, Leiby KL, Greaney AM, Yuan Y, Horien C, Linderman G, Engler AJ, Boffa DJ, Kluger Y, Rosas IO, Levchenko A, Kaminski N, Niklason LE. Single-cell connectomic analysis of adult mammalian lungs. Science Advances 2019, 5: eaaw3851. PMID: 31840053, PMCID: PMC6892628, DOI: 10.1126/sciadv.aaw3851.Peer-Reviewed Original ResearchConceptsTissue homeostasisMammalian lungSingle-cell RNA sequencing techniquesAdult mammalian lungRNA sequencing techniquesCell-cell interactionsSequencing techniquesKey pathwaysAlveolar type IFunctional roleCell typesCell populationsRegenerative medicineHomeostatic mechanismsHomeostasisFine architectureFunctional lung tissueIncomplete understandingMajor roleType ITissueRegulationPathwayAlveolar cell populationsDistal lung