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 controlsMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
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 deficiencyDeficiencyNetrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis
Sun H, Zhu Y, Pan H, Chen X, Balestrini JL, Lam TT, Kanyo JE, Eichmann A, Gulati M, Fares WH, Bai H, Feghali-Bostwick CA, Gan Y, Peng X, Moore MW, White ES, Sava P, Gonzalez AL, Cheng Y, Niklason LE, Herzog EL. Netrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis. Arthritis & Rheumatology 2016, 68: 1251-1261. PMID: 26749424, PMCID: PMC5547894, DOI: 10.1002/art.39575.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAntibodies, NeutralizingBiomechanical PhenomenaBleomycinCase-Control StudiesCell DifferentiationCollagenCollagen Type ICollagen Type I, alpha 1 ChainFibrosisFlow CytometryFluorescent Antibody TechniqueHeterozygoteHumansLeukocyte Common AntigensLeukocytes, MononuclearLungLung Diseases, InterstitialMiceMice, KnockoutMicroscopy, Electron, ScanningNerve Growth FactorsNetrin-1ProteomicsPulmonary FibrosisReverse Transcriptase Polymerase Chain ReactionScleroderma, SystemicTissue ScaffoldsTumor Suppressor ProteinsConceptsSSc-related interstitial lung diseaseInterstitial lung diseaseFibrocyte accumulationNetrin-1Lung extracellular matrixPulmonary fibrosisLung scaffoldsBleomycin-Induced Pulmonary FibrosisPeripheral blood mononuclear cellsBlood mononuclear cellsHealthy control subjectsNovel therapeutic targetSystemic sclerosisExtracellular matrixLung fibrosisLung diseaseMononuclear cellsControl subjectsLung microenvironmentHealthy controlsScleroderma patientsAberrant anatomyLung matrixPatientsTherapeutic target
2015
Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease
Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, Gulati M, Gochuico BR, Gahl WA, Slade ML, Lee CG, Elias JA. Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease. Journal Of Clinical Investigation 2015, 125: 3178-3192. PMID: 26121745, PMCID: PMC4563747, DOI: 10.1172/jci79792.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAdultAnimalsApoptosisBiomarkersChitinase-3-Like Protein 1Disease Models, AnimalFemaleGlycoproteinsHermanski-Pudlak SyndromeHumansInterleukin-13 Receptor alpha2 SubunitLectinsMaleMiceMice, KnockoutPulmonary FibrosisReceptors, ImmunologicReceptors, ProstaglandinRespiratory MucosaConceptsHermansky-Pudlak syndromePulmonary fibrosisChitinase 3Pulmonary fibrosis progressionFibroproliferative repairCHI3L1 levelsFibrosis progressionLung diseaseHPS-4HPS patientsIL-13Rα2Effector functionsReceptor CRTH2Epithelial apoptosisFibrosisProtective roleDisease severityPotential biomarkersCHI3L1Major causeHPS-1Abnormal localizationPatientsCell deathSeverity
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role
2012
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse modelChitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling
Lee CG, Herzog EL, Ahangari F, Zhou Y, Gulati M, Lee CM, Peng X, Feghali-Bostwick C, Jimenez SA, Varga J, Elias JA. Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling. The Journal Of Immunology 2012, 189: 2635-2644. PMID: 22826322, PMCID: PMC4336775, DOI: 10.4049/jimmunol.1201115.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseTGF-β1 signalingPulmonary fibrosisLung diseaseTherapeutic targetScleroderma-Associated Interstitial Lung DiseaseDifferent patient cohortsTGF-β receptor 1Wild-type miceTGF-β1 effectsSSc-ILDLung involvementSSc patientsSystemic sclerosisPulmonary responseLung fibrosisPoor prognosisCHIT1 activityPatient cohortPathogenetic mechanismsReceptor expressionMurine modelingTGF-β1Disease severityPotential biomarkers
2011
Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease
Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK, Homer R, Gulati M, Siner J, Elias J, Bucala R, Herzog E. Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease. Arthritis & Rheumatism 2011, 63: 2484-2494. PMID: 21484765, PMCID: PMC3651701, DOI: 10.1002/art.30386.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsInterstitial lung diseaseBone marrow-derived cellsMarrow-derived cellsSemaphorin 7AGrowth factor-β1Lung diseaseLung fibrosisFactor-β1Human peripheral blood mononuclear cellsNormal human peripheral blood mononuclear cellsSemaphorin 7a expressionBone marrow transplantationBlood mononuclear cellsReceptor β1 integrinΒ1 integrinFibrocyte differentiationMarrow transplantationPulmonary fibrosisMononuclear cellsProfibrotic effectsTGFβ1 geneMurine modelFibrosisTissue accumulation
2010
TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P
Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, Elias JA, Hogaboam CM, Herzog EL. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. The International Journal Of Biochemistry & Cell Biology 2010, 43: 154-162. PMID: 21044893, DOI: 10.1016/j.biocel.2010.10.013.Peer-Reviewed Original ResearchConceptsSerum amyloid PAnti-fibrotic effectsLung fibrosisFibrocyte accumulationAmyloid PAberrant extracellular matrix (ECM) depositionTransgenic mouse modelM2 macrophage differentiationPleiotropic growth factorExtracellular matrix depositionAirway inflammationIPF patientsAirway remodelingPulmonary fibrosisMacrophage accumulationLung diseaseLiposomal clodronateCXCL10 expressionM2 macrophagesMonocyte responsePulmonary macrophagesMouse modelCollagen depositionPathogenic mechanismsDisease severitySerum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages
Murray LA, Rosada R, Moreira AP, Joshi A, Kramer MS, Hesson DP, Argentieri RL, Mathai S, Gulati M, Herzog EL, Hogaboam CM. Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages. PLOS ONE 2010, 5: e9683. PMID: 20300636, PMCID: PMC2837381, DOI: 10.1371/journal.pone.0009683.Peer-Reviewed Original ResearchConceptsSerum amyloid PPulmonary fibrosisAmyloid PIPF/UIP patientsBleomycin-Induced Pulmonary FibrosisIP10/CXCL10Fibrotic lung diseaseAberrant collagen depositionRole of macrophagesM2 macrophage phenotypeUIP patientsLung diseaseM2 macrophagesCollagen depositionTissue fibrosisMacrophage activationMacrophage phenotypeFcgamma receptorsMacrophage responsePentraxin familyTherapeutic actionFibrosisMacrophagesLungTissue remodeling