2024
Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.
Trujillo G, Regueiro-Ren A, Liu C, Hu B, Sun Y, Ahangari F, Fiorini V, Ishikawa G, Al Jumaily K, Khoury J, McGovern J, Lee C, Peng X, Pivarnik T, Sun H, Walia A, Woo S, Yu S, Antin-Ozerkis D, Sauler M, Kaminski N, Herzog E, Ryu C. Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 39189851, DOI: 10.1164/rccm.202401-0065oc.Peer-Reviewed Original ResearchToll-like receptor 9Model of pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary fibrosisFibroproliferative responseLung diseaseIdiopathic pulmonary fibrosis cohortsExpression of toll-like receptor 9Toll-like receptor 9 activationTransplant-free survivalExpression of MCP-1Cohort of patientsSlow clinical progressionFibrotic lung diseaseAccelerated disease courseFatal lung diseaseIP-10Pharmacodynamic endpointsPreclinical modelsDisease courseClinical progressionPlasma mtDNAMCP-1Receptor 9Mouse modelSingle 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 transcriptomics
2023
Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease
Woo S, Gandhi S, Ghincea A, Saber T, Lee C, Ryu C. Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease. Frontiers In Cell And Developmental Biology 2023, 11: 1254904. PMID: 37849737, PMCID: PMC10577231, DOI: 10.3389/fcell.2023.1254904.Peer-Reviewed Original ResearchSSc-ILDNLRP3 inflammasomeScleroderma-Associated Interstitial Lung DiseaseAssociated interstitial lung diseaseInterstitial lung diseaseNormal lung architectureImproved treatment optionsProgressive fibrotic replacementNovel pathophysiologic insightsComplex rheumatic diseasesImmune dysregulationPathophysiologic insightsRheumatic diseasesClinical benefitIL-18IL-1βLung diseaseTreatment optionsFibrotic replacementLung architectureNovel therapiesClinical significanceInnate immunityDiseaseAdditional studiesMitochondrial DNA-Sensing Pathogen Recognition Receptors in Systemic Sclerosis-Associated Interstitial Lung Disease: a Review
Ghincea A, Woo S, Yu S, Pivarnik T, Fiorini V, Herzog E, Ryu C. Mitochondrial DNA-Sensing Pathogen Recognition Receptors in Systemic Sclerosis-Associated Interstitial Lung Disease: a Review. Current Treatment Options In Rheumatology 2023, 9: 204-220. PMID: 38230363, PMCID: PMC10791121, DOI: 10.1007/s40674-023-00211-1.Peer-Reviewed Original ResearchToll-like receptor 9Interstitial lung diseaseLung diseaseSystemic Sclerosis-Associated Interstitial Lung DiseaseAberrant innate immune activationRecent FindingsRecent advancesCause of morbidityInnate immune activationNovel treatment approachesPathogen recognition receptorsCyclic guanosine monophosphate-adenosine monophosphate synthaseReviewSystemic sclerosisSSc patientsImmune dysregulationImmune activationReceptor 9Inflammatory fibrosisScar formationTreatment approachesRecognition receptorsDiseaseImportant unanswered questionsMechanism of releaseReviewUnanswered questions
2022
Emerging insights in sarcoidosis: moving forward through reverse translational research
Liu A, Sharma L, Yan X, Dela Cruz CS, Herzog EL, Ryu C. Emerging insights in sarcoidosis: moving forward through reverse translational research. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2022, 322: l518-l525. PMID: 35196896, PMCID: PMC8957321, DOI: 10.1152/ajplung.00266.2021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTranslational researchFibrotic lung diseasePulmonary granuloma formationReverse translational researchChronic granulomatous diseaseImmunopathogenic mechanismsLung diseaseUnknown etiologyGranulomatous diseaseGranuloma formationSarcoidosis researchStage IVDisease pathogenesisClinical phenotypeSarcoidosisClinical interventionsDisease model developmentFibrogenesisSignificant proportionFundamental mediatorDiseaseFurther investigationInvestigative effortsHypothesis-driven researchMorbidityAn Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report
Ghincea A, Ryu C, Herzog EL. An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report. CHEST Journal 2022, 161: e71-e73. PMID: 35131075, PMCID: PMC8814523, DOI: 10.1016/j.chest.2021.07.2160.Peer-Reviewed Case Reports and Technical NotesConceptsIdiopathic pulmonary fibrosisAE-IPFAcute exacerbationPulmonary fibrosisLung diseaseCase reportFatal interstitial lung diseaseMRNA COVID-19 vaccinationChronic lung diseaseInterstitial lung diseaseVaccine-preventable diseasesNovel case reportA Case ReportCOVID-19 vaccinationScar tissue formationRespiratory decompensationAdverse eventsPulmonary embolismVulnerable patientsDrug toxicityPotential associationShort courseDiseaseExacerbationFibrosis
2021
Case Report: Bullous Lung Disease Following COVID-19
Pednekar P, Amoah K, Homer R, Ryu C, Lutchmansingh DD. Case Report: Bullous Lung Disease Following COVID-19. Frontiers In Medicine 2021, 8: 770778. PMID: 34869488, PMCID: PMC8635639, DOI: 10.3389/fmed.2021.770778.Peer-Reviewed Case Reports and Technical NotesSARS-CoV-2 infectionBullous lung diseaseCoV-2 infectionRadiological abnormalitiesLung diseaseAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCoronavirus 2 infectionInterlobular septal thickeningPost-acute sequelaeGround-glass opacitiesFibrotic-like changesCoronavirus disease 2019COVID-19Mosaic attenuationSeptal thickeningSymptom onsetPulmonary diseaseRespiratory manifestationsParenchymal bandsCase reportDisease 2019InfectionDisease
2020
Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Ryu C, Walia A, Ortiz V, Perry C, Woo S, Reeves BC, Sun H, Winkler J, Kanyo JE, Wang W, Vukmirovic M, Ristic N, Stratton EA, Meena SR, Minasyan M, Kurbanov D, Liu X, Lam TT, Farina G, Gomez JL, Gulati M, Herzog EL. Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease. Arthritis & Rheumatology 2020, 72: 1905-1915. PMID: 32602227, PMCID: PMC8081728, DOI: 10.1002/art.41418.Peer-Reviewed Original ResearchConceptsCGAS/STING activationExtracellular vesiclesMitochondrial DNAPattern recognition receptorsCyclic GMP-AMP synthase/stimulatorHuman lung fibroblastsSSc-ILD cohortsInterstitial lung diseaseMT-ATP6 geneΑ-SMA expressionI interferonSSc-ILDScleroderma-Associated Interstitial Lung DiseaseSynthetic CpG DNATLR-9Clinical outcomesLung diseaseSTING activationInterleukin-6Enzyme-linked immunosorbent assay-based methodProteomic profilesMulticellular originSystemic sclerosis-associated interstitial lung diseaseImmune pattern recognition receptorsExtracellular mtDNASerum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis
Sakamoto K, Furukawa T, Yamano Y, Kataoka K, Teramachi R, Walia A, Suzuki A, Inoue M, Nakahara Y, Ryu C, Hashimoto N, Kondoh Y. Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis. European Respiratory Journal 2020, 57: 2001346. PMID: 32855220, PMCID: PMC8177039, DOI: 10.1183/13993003.01346-2020.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAcute exacerbationPulmonary fibrosisDisease progressionFatal interstitial lung diseaseInterstitial lung diseaseSerum mitochondrial DNAAccepted biomarkersClinical deteriorationMedian survivalDeadly complicationDisease courseLethal complicationLung functionLung diseaseUnknown etiologyExacerbationUnmet needProgressionComplicationsRapid deteriorationPatientsFibrosisDevastating diseaseDisease
2019
GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis
Zhang Y, Jiang M, Nouraie M, Roth MG, Tabib T, Winters S, Chen X, Sembrat J, Chu Y, Cardenes N, Tuder RM, Herzog EL, Ryu C, Rojas M, Lafyatis R, Gibson KF, McDyer JF, Kass DJ, Alder JK. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l510-l521. PMID: 31432710, PMCID: PMC6842909, DOI: 10.1152/ajplung.00062.2019.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlveolar Epithelial CellsAnimalsBleomycinBronchoalveolar Lavage FluidCase-Control StudiesDisease Models, AnimalFemaleGene Expression ProfilingGrowth Differentiation Factor 15HumansIdiopathic Pulmonary FibrosisLungMaleMiceMiddle AgedRespiratory Function TestsSeverity of Illness IndexSurvival AnalysisTelomereTranscriptomeConceptsIdiopathic pulmonary fibrosisBleomycin challengePulmonary fibrosisEpithelial cellsDisease pathologyConcentrations of GDF15Type II alveolar epithelial cellsInterstitial lung diseaseDifferentiation factor 15Multiple independent cohortsAlveolar epithelial cellsLung epithelial cellsIPF patientsPulmonary functionBronchoalveolar lavagePoor outcomeLung diseasePeripheral bloodEpithelial dysfunctionTelomere dysfunctionLung tissueFactor 15Epithelial stressIndependent cohortUseful biomarkerChitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee CM, He CH, Park JW, Lee JH, Kamle S, Ma B, Akosman B, Cotez R, Chen E, Zhou Y, Herzog EL, Ryu C, Peng X, Rosas IO, Poli S, Bostwick CF, Choi AM, Elias JA, Lee CG. Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2019, 2: e201900350. PMID: 31085559, PMCID: PMC6516052, DOI: 10.26508/lsa.201900350.Peer-Reviewed Original ResearchMeSH KeywordsFibroblastsForkhead Box Protein O3Gene Expression RegulationGenes, ReporterHexosaminidasesHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsPromoter Regions, GeneticPulmonary FibrosisRNA, Small InterferingSignal TransductionSmad7 ProteinTransforming Growth Factor betaConceptsTGF-β1 signalingPulmonary fibrosisTGF-β1 inductionTGF-β1Idiopathic pulmonary fibrosisInterstitial lung diseaseTGF-β1/TGF-β receptorLung diseaseEffector responsesFibrotic responseTissue fibrosisFibrosisCritical mediatorCritical roleBox O3Protein 1DiseaseSmad7Tissue responseFOXO3TGFBRAP1Chitinase 1InductionPathwayCirculating Mitochondrial DNA Is Associated with Fibroblast Activation and Disease Progression in Scleroderma Associated Interstitial Lung Disease
Ryu C, Sun H, Winkler J, Meena S, Walia A, Minasyan M, Brandsdorfer C, Gulati M, Peng X, Herzog E. Circulating Mitochondrial DNA Is Associated with Fibroblast Activation and Disease Progression in Scleroderma Associated Interstitial Lung Disease. 2019, a7219-a7219. DOI: 10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7219.Peer-Reviewed Original Research
2016
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiency