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 transcriptomics
2023
microRNA-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
2021
Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controls
2020
Reduced 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
Plasma 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 insights
2017
Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis
Murray LA, Habiel DM, Hohmann M, Camelo A, Shang H, Zhou Y, Coelho AL, Peng X, Gulati M, Crestani B, Sleeman MA, Mustelin T, Moore MW, Ryu C, Osafo-Addo AD, Elias JA, Lee CG, Hu B, Herazo-Maya JD, Knight DA, Hogaboam CM, Herzog EL. Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis. JCI Insight 2017, 2: e92192. PMID: 28814671, PMCID: PMC5621899, DOI: 10.1172/jci.insight.92192.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisPulmonary fibrosisEndothelial cell-derived mediatorsThrombospondin-1Chronic progressive declineIntratracheal bleomycin challengeVEGF transgenic miceCell-derived mediatorsLung-specific overexpressionVascular endothelial growth factorEpithelial cell injuryLevels of VEGFAssociation of VEGFEndothelial growth factorImpaired restitutionBleomycin challengeIPF pathogenesisLung functionEpithelial wound closureLung fibrosisAntifibrotic roleHealthy controlsPreclinical modelsProgressive phenotypeCell injury
2016
Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis
Tzouvelekis A, Herazo‐Maya J, Slade M, Chu J, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin‐Ozerkis D, Herzog EL, Kaminski N. Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis. Respirology 2016, 22: 486-493. PMID: 27761978, PMCID: PMC5352520, DOI: 10.1111/resp.12920.Peer-Reviewed Original ResearchConceptsTransplant-free survivalIdiopathic pulmonary fibrosisMMP-7 concentrationsMatrix metalloproteinase-7IPF patientsCause mortalityPulmonary fibrosisHealthy controlsMultivariate Cox proportional hazards modelCox proportional hazards modelPulmonary function parametersVariable clinical courseBaseline pulmonary function parametersProportional hazards modelIPF biomarkersProgressive diseaseClinical coursePoor prognosisPrognostic valueVital capacityIndependent biomarkerLung capacityPrognostic thresholdPlasma concentrationsMortality risk