2024
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virus
2023
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Schupp J, Manning E, Chioccioli M, Kamp J, Christian L, Ryu C, Herzog E, Kühnel M, Prasse A, Kaminski N, Jonigk D, Homer R, Neubert L, Ius F, stringJustet A, Hariri L, Seeliger B, Welte T, Knipe R, Gottlieb J. Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 819-822. PMID: 37552025, PMCID: PMC10563189, DOI: 10.1164/rccm.202303-0544le.Peer-Reviewed Original ResearchTLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance
Çakan E, Kioon M, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Loza A, Du Y, Schickel J, Boeckers J, Yang C, Baldo A, Ivashkiv L, Young R, Staudt L, Moody K, Nündel K, Marshak-Rothstein A, van der Made C, Hoischen A, Hayward A, Rossato M, Radstake T, Cunningham-Rundles C, Ryu C, Herzog E, Barrat F, Meffre E. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. Journal Of Experimental Medicine 2023, 220: e20230944. PMID: 37773045, PMCID: PMC10541333, DOI: 10.1084/jem.20230944.Peer-Reviewed Original ResearchConceptsCentral B cell toleranceB cell toleranceCell toleranceB cellsSystemic sclerosisTLR9 functionNovel therapeutic strategiesTLR9/MyD88Immature B cellsB cell receptorTolerogenic functionSSc patientsTLR9 expressionHumanized miceTLR9 responsesAutoreactive clonesTherapeutic strategiesChemokine CXCL4Cell receptorCXCL4Vivo productionTLR9MyD88ReceptorsCellsmicroRNA-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 mouseα1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis
Ishikawa G, Peng X, McGovern J, Woo S, Perry C, Liu A, Yu S, Ghincea A, Kishchanka A, Fiorini V, Hu B, Sun Y, Sun H, Ryu C, Herzog E. α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2023, 324: l639-l651. PMID: 36648147, PMCID: PMC10110730, DOI: 10.1152/ajplung.00119.2022.Peer-Reviewed Original ResearchConceptsAdrenergic nerve supplyIdiopathic pulmonary fibrosisΑ1 adrenoreceptorsPulmonary fibrosisNerve supplyCultured normal human lung fibroblastsInnate immune ligandsLung fibrosis modelNormal human lung fibroblastsSmooth muscle actinHuman lung fibroblastsAdrenal resectionAdrenoreceptor antagonismExtracellular mtDNAIPF cohortImproved survivalΑ1-adrenoreceptor antagonistsLung fibrosisAdrenal sourceFibroblast accumulationAdrenoreceptor antagonistBleomycin modelFibrosis modelLung fibrogenesisMouse model
2022
Occupational and environmental exposures in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study
Ryan SM, Mroz MM, Herzog EL, Ryu C, Fingerlin TE, Maier LA, Gulati M. Occupational and environmental exposures in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Respiratory Medicine 2022, 200: 106923. PMID: 35932543, DOI: 10.1016/j.rmed.2022.106923.Peer-Reviewed Original ResearchConceptsAlpha-1 antitrypsin deficiencyCardiac sarcoidosisSarcoidosis StudyAntitrypsin deficiencyRadiation exposureNon-cardiac sarcoidosisNon-chronic diseasesMultiple comparisonsEnvironmental exposure dataExtrapulmonary diseasePulmonary involvementGranulomatous disorderSarcoidosis phenotypesRisk factorsSpecific disease phenotypesStage 0Number of exposuresSarcoidosisExposure assessment toolsSusceptible individualsSpecific exposuresDiseaseEnvironmental exposuresExposure dataIndividual exposureInhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis
Damsky W, Wang A, Kim DJ, Young BD, Singh K, Murphy MJ, Daccache J, Clark A, Ayasun R, Ryu C, McGeary MK, Odell ID, Fazzone-Chettiar R, Pucar D, Homer R, Gulati M, Miller EJ, Bosenberg M, Flavell RA, King B. Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nature Communications 2022, 13: 3140. PMID: 35668129, PMCID: PMC9170782, DOI: 10.1038/s41467-022-30615-x.Peer-Reviewed Original ResearchConceptsType 1 immunityInternal organ involvementOrgan involvementT cell-derived IFNIdiopathic inflammatory disorderOpen-label trialMonths of treatmentType 1 cytokinesJanus kinase inhibitorImmunologic changesLongstanding sarcoidosisSarcoidosis activitySarcoidosis symptomsClinical improvementCutaneous sarcoidosisSecondary outcomesComplete responsePrimary outcomeTofacitinib treatmentActivity scoreCytokine mediatorsIL-12IL-15IL-6Inflammatory disordersEmerging 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
Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones
Glauzy S, Olson B, May CK, Parisi D, Massad C, Hansen JE, Ryu C, Herzog EL, Meffre E. Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones. Arthritis & Rheumatology 2021, 74: 307-317. PMID: 34279059, PMCID: PMC8766600, DOI: 10.1002/art.41927.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsEarly B cell tolerance checkpointsPeripheral B cell tolerance checkpointsNaive B cellsMature naive B cellsSystemic sclerosisTransitional B cellsTolerance checkpointsB cellsHealthy donorsAutoreactive mature naive B cellsAutoreactive naive B cellsAntigen-specific B cellsCentral B cell toleranceB cell toleranceB cell productionAntigen-specific clonesReactivity of antibodiesSingle B cellsSSc patientsSerum autoantibodiesAutoimmune diseasesImmune complexesPatientsCell tolerance
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 diseaseDiseaseA 50-Year-Old Woman With Limited Scleroderma Presenting With Shortness of Breath
Walia A, Singh I, Ryu C, Lutchmansingh DD. A 50-Year-Old Woman With Limited Scleroderma Presenting With Shortness of Breath. CHEST Journal 2020, 158: e37-e40. PMID: 32654737, PMCID: PMC8097629, DOI: 10.1016/j.chest.2020.02.041.Peer-Reviewed Original ResearchConceptsInterstitial lung diseasePulmonary arterial pressurePulmonary arterial hypertensionArterial hypertensionMycophenolate mofetilLimited sclerodermaArterial pressureCalculated pulmonary vascular resistanceMean pulmonary arterial pressureSevere pulmonary arterial hypertensionStable interstitial lung diseasePulmonary arterial wedge pressureLow-dose prednisonePulmonary vascular resistanceRight heart catheterizationRight atrial pressureLower extremity edemaRight ventricular pressureChronic shortnessCardiac indexChest painHeart catheterizationSick contactsVascular resistanceWedge pressureReduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis
Chen W, Karhadkar TR, Ryu C, Herzog EL, Gomer RH. Reduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis. ImmunoHorizons 2020, 4: 352-362. PMID: 32576593, PMCID: PMC8500545, DOI: 10.4049/immunohorizons.2000043.Peer-Reviewed Original ResearchConceptsSerum amyloid PIPF patientsPulmonary fibrosisFibrocyte differentiationIL-10 accumulationAmyloid PEffects of SAPIdiopathic pulmonary fibrosis (IPF) pathogenesisPulmonary fibrosis pathogenesisIdiopathic pulmonary fibrosisBronchoalveolar lavage fluidSera of patientsHigh extracellular levelsPotential therapeutic targetDifferentiation of monocytesSialic acidIPF pathogenesisIL-10Scar-like tissueLavage fluidHealthy controlsFatal disorderFibrosis pathogenesisHuman PBMCsTherapeutic target
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 biomarkerPlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insightsNew Applications of Old Drugs as Novel Therapies in Idiopathic Pulmonary Fibrosis. Metformin, Hydroxychloroquine, and Thyroid Hormone
Manning EP, Losier A, Emeagwali N, Ryu C, Honiden S. New Applications of Old Drugs as Novel Therapies in Idiopathic Pulmonary Fibrosis. Metformin, Hydroxychloroquine, and Thyroid Hormone. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 1561-1563. PMID: 30822095, PMCID: PMC7051474, DOI: 10.1164/rccm.201809-1700rr.Peer-Reviewed Original ResearchChitinase 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 1InductionPathway
2018
S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension
Tzouvelekis A, Herazo‐Maya J, Ryu C, Chu J, Zhang Y, Gibson KF, Adonteng‐Boateng P, Li Q, Pan H, Cherry B, Ahmad F, Ford HJ, Herzog EL, Kaminski N, Fares WH. S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension. Respirology 2018, 23: 771-779. PMID: 29611244, PMCID: PMC6047907, DOI: 10.1111/resp.13302.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsPH patientsPH cohortCardiac outputWorld Health Organization group 1Idiopathic pulmonary fibrosis patientsPulmonary hypertension patientsPulmonary fibrosis patientsBlood mononuclear cellsProtein serum concentrationsHigher S100A12Pulmonary hypertensionS100A12 levelsOverall mortalityHypertension patientsPrognostic valueValidation cohortMononuclear cellsPeripheral bloodSerum concentrationsInflammatory diseasesGroup 1PatientsFibrosis patientsS100A12A novel endobronchial approach to massive hemoptysis complicating silicone Y-stent placement for tracheobronchomalacia
Ryu C, Boffa D, Bramley K, Pisani M, Puchalski J. A novel endobronchial approach to massive hemoptysis complicating silicone Y-stent placement for tracheobronchomalacia. Medicine 2018, 97: e9980. PMID: 29465600, PMCID: PMC5842006, DOI: 10.1097/md.0000000000009980.Peer-Reviewed Original ResearchConceptsOxidized regenerated celluloseSilicone YBronchial limbMassive hemoptysisStent placementLife-threatening hemoptysisGranulation tissue formationLong-term managementSurgical sealantEmergent bronchoscopySymptomatic tracheobronchomalaciaAirway stabilizationEndobronchial therapyMucus pluggingCommon complicationInitial hemostasisSufficient hemostasisAirway wallRare caseEndobronchial approachTracheobronchomalaciaHemoptysisPulsatile vesselsComplete cessationSubsequent placement