2025
CD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Carter H, Costa R, Adams T, Gilchrist T, Emch C, Bame M, Oldham J, Huang S, Linderholm A, Noth I, Kaminski N, Moore B, Gurczynski S. CD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis. JCI Insight 2025, 10 PMID: 39964756, PMCID: PMC11949071, DOI: 10.1172/jci.insight.177072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBasic Helix-Loop-Helix Transcription FactorsBleomycinDendritic CellsDisease Models, AnimalFibroblastsHumansIdiopathic Pulmonary FibrosisIntegrin alpha ChainsInterleukin-6LungMaleMiceMice, Inbred C57BLReceptors, Aryl HydrocarbonSignal TransductionToll-Like Receptor 9Tryptophan OxygenaseConceptsIdiopathic pulmonary fibrosisAhR signalingMice treated with BLMIL-17+ cellsCD103+ DCLoss of lung functionStudies of human samplesLimited treatment optionsTreated ex vivoProduction of IL-6Inflammatory cytokine productionExon 2 deletionExpression of TDO2IL-6 productionAdoptive transferCD11c-CreCD11c+ cellsImmunological changesPulmonary fibrosisTLR agonistsProgressive scarringTreatment optionsCytokine productionLung fibrogenesisAryl hydrocarbon receptor
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 ResearchMeSH KeywordsAnimalsBleomycinChemokine CXCL6ChemokinesCollagenFibroblastsHumansIdiopathic Pulmonary FibrosisLungMiceConceptsIdiopathic 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 sequencingVISTA (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 target
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 ResearchMeSH KeywordsAnimalsDisease Models, AnimalFibroblastsFibrosisHumansIdiopathic Pulmonary FibrosisLungMicePhenotypeConceptsIdiopathic 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 inhibitorMicroenvironmental sensing by fibroblasts controls macrophage population size
Zhou X, Franklin RA, Adler M, Carter TS, Condiff E, Adams TS, Pope SD, Philip NH, Meizlish ML, Kaminski N, Medzhitov R. Microenvironmental sensing by fibroblasts controls macrophage population size. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2205360119. PMID: 35930670, PMCID: PMC9371703, DOI: 10.1073/pnas.2205360119.Peer-Reviewed Original ResearchConceptsCell typesDensity-dependent gene expressionTGF-β target genesDiverse cell typesActin-dependent mechanismLineage-specific growth factorsDistinct cell typesGrowth factor availabilityActivation of YAP1Different cell typesExpression programsMicroenvironmental sensingTranscriptional coactivatorTarget genesGene expressionPopulation sizeFactor availabilityPopulation numbersTissue environmentTissue integrityHippoProliferation of macrophagesYAP1Animal tissuesMechanical forces
2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesisFibroblasts 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
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