2024
Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nekola 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 PMID: 38924775, 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 transcriptomicsNoninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1
Mannes P, Adams T, Farsijani S, Barnes C, Latoche J, Day K, Nedrow J, Ahangari F, Kaminski N, Lee J, Tavakoli S. Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1. Science Advances 2024, 10: eadm9817. PMID: 38896611, PMCID: PMC11186491, DOI: 10.1126/sciadv.adm9817.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisFibrotic lung diseaseRisk stratificationMurine modelLung fibrosisLung diseaseModel of bleomycin-induced lung fibrosisBleomycin-induced lung fibrosisImaging biomarkersMurine model of bleomycin-induced lung fibrosisBronchoalveolar lavage cellsMonocyte-derived macrophagesPositron emission tomographyInflammatory endotypesPulmonary fibrosisLavage cellsPoor survivalNoninvasive assessmentTherapeutic monitoringEmission tomographyCMKLR1FibrosisClinical trajectoryLungLung regions
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 ResearchConceptsIdiopathic 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 targetmicroRNA-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
Airway 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 inhibitorCD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Cui H, Xie N, Banerjee S, Dey T, Liu RM, Antony VB, Sanders YY, Adams TS, Gomez JL, Thannickal VJ, Kaminski N, Liu G. CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 459-475. PMID: 35687485, DOI: 10.1164/rccm.202109-2151oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung fibrosisCD38 expressionAlveolar epithelial cell injuryEpithelial cell injuryEffective therapeutic strategyHuman lung parenchymaIPF lungsLung functionPulmonary fibrosisDisease progressionFibrotic lungsReal-time PCRYoung miceLung parenchymaOld miceCell injuryTherapeutic strategiesFibrosisPharmacological inactivationCD38Single-cell RNA sequencingFlow cytometryWestern blottingOld animalsLeveraging Cell-Specific Disease Signatures to Predict New Drug Therapies for Idiopathic Pulmonary Fibrosis
Adams T, Song Q, Justet A, Mcdonough J, DeIuliis G, Yan X, Bar-Joseph Z, Kaminski N. Leveraging Cell-Specific Disease Signatures to Predict New Drug Therapies for Idiopathic Pulmonary Fibrosis. 2022, a2318-a2318. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2318.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisNew drug therapiesPulmonary fibrosisDrug therapyDisease signaturesFibrosisTherapy
2021
Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis
Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y. Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis. European Respiratory Journal 2021, 58: 2003397. PMID: 34049947, DOI: 10.1183/13993003.03397-2020.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisAnti-fibrotic propertiesRole of fibroblastsFibroblastic fociPathogenesis of IPFLung fibrosis modelSenescence-associated secretory phenotypeNormal lung samplesMesenchymal stromal cellsIPF patientsIPF lungsDense fibrosisPathological hallmark lesionsFibrosis modelFibrotic lungsHallmark lesionsSingle-cell atlasActive fibrogenesisElderly individualsLung samplesFibrosisSingle-cell RNA sequencingFibrotic regionsSecretory phenotype