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, 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, PMCID: PMC11568434, 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
Mitochondrial 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 questionsRational engineering of lung alveolar epithelium
Leiby K, Yuan Y, Ng R, Raredon M, Adams T, Baevova P, Greaney A, Hirschi K, Campbell S, Kaminski N, Herzog E, Niklason L. Rational engineering of lung alveolar epithelium. Npj Regenerative Medicine 2023, 8: 22. PMID: 37117221, PMCID: PMC10147714, DOI: 10.1038/s41536-023-00295-2.Peer-Reviewed Original Research
2022
Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants
Mlakar L, Garrett S, Watanabe T, Sanderson M, Nishimoto T, Heywood J, Helke K, Pilewski J, Herzog E, Feghali-Bostwick C. Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants. Biomedicines 2022, 10: 2861. PMID: 36359382, PMCID: PMC9687961, DOI: 10.3390/biomedicines10112861.Peer-Reviewed Original ResearchAnti-fibrotic effectsIdiopathic pulmonary fibrosisSystemic sclerosisPulmonary fibrosisLung fibrosisMouse modelSignificant anti-fibrotic effectEffective anti-fibrotic therapiesBleomycin mouse modelLungs of patientsAnti-fibrotic therapiesPrevention of skinSecond mouse modelCollagen XVIII/endostatinGrowth factor-β1Matrix-degrading enzymesLung transplantationSignificant morbidityHuman tissuesLung diseaseHealth burdenEffective treatmentFactor-β1Organ fibrosisFibrosisAdaptive Immunity in Interstitial Lung Disease
Winkler J, Herzog E. Adaptive Immunity in Interstitial Lung Disease. 2022, 144-157. DOI: 10.1016/b978-0-08-102723-3.00018-4.ChaptersInterstitial lung diseaseIdiopathic pulmonary fibrosisLung diseaseAdaptive immunityBasic science investigationsAutoimmune conditionsPulmonary fibrosisHumoral responseClinical observationsTranslational studiesAberrant remodelingDiseaseUnifying hypothesisImmunityUnanswered questionsImmunopathogenesisSclerodermaFibrosisInjury
2019
Circulating 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
2014
Pulmonary Fibrosis
Murray L, Homer R, Gulati M, Herzog E. Pulmonary Fibrosis. 2014, 2636-2653. DOI: 10.1016/b978-0-12-386456-7.05307-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInterstitial lung diseasePulmonary fibrosisLung fibrosisConnective tissue disease-related interstitial lung diseaseIdiopathic pulmonary fibrosisSalient clinical featuresDistinctive pathological featuresWound healing responseClinical featuresChronic injuryLung diseasePathological featuresCirculating BiomarkersInflammatory responseLung parenchymaCertain therapiesPathogenic mechanismsScar tissueClinical monitoringFibrosisHealing responseFatal natureGenetic formsDiseasePotential role
2013
Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials
Saketkoo L, Mittoo S, Huscher D, Khanna D, Dellaripa P, Distler O, Flaherty K, Frankel S, Oddis C, Denton C, Fischer A, Kowal-Bielecka O, LeSage D, Merkel P, Phillips K, Pittrow D, Swigris J, Antoniou K, Baughman R, Castelino F, Christmann R, Christopher-Stine L, Collard H, Cottin V, Danoff S, Highland K, Hummers L, Shah A, Kim D, Lynch D, Miller F, Proudman S, Richeldi L, Ryu J, Sandorfi N, Sarver C, Wells A, Strand V, Matteson E, Brown K, Seibold J, Aggarwal* R, Ainslie G, Alkassab F, Allanore Y, Descartes P, Anderson M, Andonopoulos A, Antin-Ozerkis D, Arrobas A, Ascherman* D, Assassi S, Baron M, Bathon* J, Behr J, Beretta L, Bingham C, Binnie M, Birring S, Boin F, Bongartz* T, Bourdin A, Bouros D, Brasington R, Bresser P, Buch M, Burge P, Carmona L, Carreira P, Carvalho C, Catoggio L, Chan K, Chapman J, Chatterjee S, Chua* F, Chung L, Conron M, Corte T, Cosgrove G, Costabel U, Cox G, Crestani B, Crofford L, Csuka M, Curbelo P, László C, Daniil Z, D'Arsigny C, Davis G, de Andrade J, De Vuyst P, Dempsey O, Derk C, Distler J, Dixon* W, Downey G, Doyle M, Drent M, Durairaj L, Emery P, Espinoza L, Farge D, Fathi M, Fell C, Fessler B, Fitzgerald J, Fox G, Foeldvari I, Frech T, Freitas S, Furst* D, Gabrielli A, García-Vicuña R, Georgiev O, Gerbino A, Gillisen A, Gladman D, Glassberg M, Gochuico B, Gogali A, Goh* N, Goldberg A, Goldberg H, Gourley* M, Griffing L, Grutters J, Gunnarsson R, Hachulla E, Hall F, Harari S, Herrick A, Herzog E, Hesselstrand R, Hirani N, Hodgson U, Hollingsworth H, Homer R, Hoyles R, Hsu V, Hubbard R, Hunzelmann N, Isasi M, Isasi E, Jimenez J, Johnson S, Jones C, Kahaleh B, Kairalla R, Kalluri M, Kalra S, Kaner R, Kinder B, Klingsberg R, Kokosi M, Kolb M, Kur-Zalewska J, Kuwana* M, Lake F, Lally E, Lasky J, Laurindo I, Able L, Lee P, Leonard C, Lien D, Limper A, Liossis S, Lohr K, Loyd J, Lundberg* I, Mageto Y, Maher T, Mahmud T, Manganas H, Marie I, Marras T, Martinez J, Martinez F, Mathieu A, Matucci-Cerinic* M, Mayes* M, McKown K, Medsger T, Meehan R, Cristina M, Meyer K, Millar A, Moğulkoç N, Molitor J, Morais A, Mouthon P, Müller V, Müller-Quernheim J, Nadashkevich O, Nador R, Nash P, Nathan S, Navarro C, Neves S, Noth I, Nunes H, Olson A, Opitz C, Padilla M, Pappas D, Parfrey H, Pego-Reigosa J, Pereira C, Perez R, Pope* J, Porter J, Renzoni E, Riemekasten G, Riley D, Rischmueller M, Rodriguez-Reyna T, Rojas-Serrano, Romam J, Rosen G, Rossman M, Rothfield N, Sahn S, Sanduzzi A, Scholand M, Selman M, Senécal J, Seo P, Silver* R, Solomon J, Steen* V, Stevens W, Strange C, Sussman R, Sutton E, Sweiss N, Tornling G, Tzelepis G, Undurraga A, Vacca A, Vancheri C, Varga J, Veale D, Volkov S, Walker U, Wencel M, Wesselius L, Wickremasinghe M, Wilcox P, Wilsher M, Wollheim F, Wuyts W, Yung G, Zanon P, Zappala C, Groshong S, Leslie K, Myers J, Padera R, Desai S, Goldin J, Kazerooni E, Klein J, Lynch D, Keen K. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax 2013, 69: 436. PMID: 24368713, PMCID: PMC3995282, DOI: 10.1136/thoraxjnl-2013-204202.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisConnective tissue diseaseInterstitial lung diseaseCTD-ILDPulmonary fibrosisTissue diseaseLung diseaseClinical trialsOutcome measuresRelated interstitial lung diseaseNominal group panelHealth-related qualityPatient focus groupsMulticentre clinical trialAppropriate outcome measuresClinical trial designILD expertsDisease activityMulticentre RCTsTreatment responseLung physiologyTrial designConsensus methodologyIdentification of outcomesLung imaging
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 severityCirculating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype
Mathai SK, Gulati M, Peng X, Russell TR, Shaw AC, Rubinowitz AN, Murray LA, Siner JM, Antin-Ozerkis DE, Montgomery RR, Reilkoff RA, Bucala RJ, Herzog EL. Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Laboratory Investigation 2010, 90: 812-823. PMID: 20404807, PMCID: PMC3682419, DOI: 10.1038/labinvest.2010.73.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseSSc-ILD patientsSSc-ILDIL-10Normal controlsProfibrotic cellsSystemic sclerosisLung diseaseCollagen-producing cellsMCP-1Profibrotic phenotypeSSc-related interstitial lung diseaseFlow cytometryPeripheral blood profilesSSc-ILD cohortsIL-10 secretionSystemic sclerosis patientsExpression of CD163Blood of patientsHealthy aged controlsCultured CD14Profibrotic characteristicsProfibrotic mediatorsTNF levelsSclerosis patients