2024
Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola 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, 210: 1252-1266. 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 transcriptomicsANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE
YU S, LEE C, HU B, SUN Y, SHAO S, SUN H, GHINCEA A, WOO S, MCGOVERN J, SABER T, GUNES B, KUJAWSKI S, PEREZ S, ODELL W, HINCHCLIFF M, VARGA J, SAULER M, GOMEZ J, RYU C, HERZOG E. ANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE. CHEST Journal 2024, 166: a3380-a3381. DOI: 10.1016/j.chest.2024.06.2018.Peer-Reviewed Original ResearchRetraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cortez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2024, 7: e202402987. PMID: 39209538, PMCID: PMC11361373, DOI: 10.26508/lsa.202402987.Peer-Reviewed Original ResearchToll-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 Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantPlasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Sand J, Jessen H, Leeming D, Yu S, Lee C, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern J, Fiorini V, Saber T, Higuero-Sevilla J, Gulati M, Kaminski N, Damsky W, Shaw A, Mohanty S, Goobie G, Zhang Y, Herzog E, Ryu C. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts. Thorax 2024, 79: thorax-2023-221095. PMID: 39117421, DOI: 10.1136/thorax-2023-221095.Peer-Reviewed Original ResearchSarcoidosis cohortMultiorgan diseasePRO-C3Interleukin-4Case Control Etiologic Study of SarcoidosisPlasma levels of interleukin-4Alpha-1 antitrypsin deficiencyLevels of interleukin-4Pathogenesis of sarcoidosisC6MC3MHealthy control patientsStudy of sarcoidosisGenomic researchAbnormal extracellular matrixAssociated with dermatological diseaseCollagen degradationScadding stageCorticosteroid useComplex diseasesPRO-C6Control patientsIL-13IL-5IL-9Role of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis
Ishikawa G, Peng X, Mcgovern J, Ghincea A, Saber T, Sun H, Sauler M, Ryu C, Herzog E. Role of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis. 2024, a5206-a5206. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5206.Peer-Reviewed Original ResearchInnate Immune Effects of Α1-adrenoreceptor Antagonism in Sarcoidosis
Saber T, Yu S, Lee C, Fiorini V, Mcgovern J, Woo S, Gulati M, Ryu C, Herzog E. Innate Immune Effects of Α1-adrenoreceptor Antagonism in Sarcoidosis. 2024, a2531-a2531. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2531.Peer-Reviewed Original ResearchTelomere Attrition Is Associated With Sarcoidosis
Gandhi S, Lee C, Yu S, Saber T, Woo S, Mcgovern J, Fiorini V, Gulati M, Herzog E, Ryu C. Telomere Attrition Is Associated With Sarcoidosis. 2024, a2530-a2530. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2530.Peer-Reviewed Original ResearchIntranasal 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
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationTargeting 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 studiesAlveolar 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 productionTLR9MyD88ReceptorsCellsMitochondrial 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 questionsToll-like Receptor-9 Activation Promotes Persistent Inflammation in the Lung During Influenza Infection
Essayas H, Kim J, Mcgovern J, Peng X, Cai Y, Ishikawa G, Herzog E, Dela Cruz C, Ryu C, Sharma L. Toll-like Receptor-9 Activation Promotes Persistent Inflammation in the Lung During Influenza Infection. 2023, a5608-a5608. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a5608.Peer-Reviewed Original ResearchCorrection: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cotez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Correction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2023, 6: e202302065. PMID: 37037591, PMCID: PMC10088146, DOI: 10.26508/lsa.202302065.Peer-Reviewed Original ResearchmicroRNA-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 exposure