2024
Single-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 chemoattractantSingle-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
2022
Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells
Sumida TS, Dulberg S, Schupp JC, Lincoln MR, Stillwell HA, Axisa PP, Comi M, Unterman A, Kaminski N, Madi A, Kuchroo VK, Hafler DA. Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Nature Immunology 2022, 23: 632-642. PMID: 35301508, PMCID: PMC8989655, DOI: 10.1038/s41590-022-01152-y.Peer-Reviewed Original ResearchConceptsCoinhibitory receptor expressionHuman T cellsIFN-I responsesCoinhibitory receptorsT cellsTIGIT expressionReceptor expressionAcute SARS-CoV-2 infectionPD-1/TimSARS-CoV-2 infectionEnhancement of immunotherapyType 1 interferonT-cell featuresLAG-3Infectious diseasesDifferent temporal kineticsTranscription factorsCancer therapyReceptorsCell featuresKey transcription factorIFNPresent studyMRNA profilingKey regulatorSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2018
Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis
McDonough JE, Kaminski N, Thienpont B, Hogg JC, Vanaudenaerde BM, Wuyts WA. Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis. Thorax 2018, 74: 132. PMID: 30366970, PMCID: PMC6467239, DOI: 10.1136/thoraxjnl-2018-211929.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung functionPulmonary fibrosisExtensive pathological changesSevere lung diseaseLung Tissue Research ConsortiumCorrelation network analysisIPF cohortIPF groupLung diseaseControl subjectsUpregulated modulesT cellsImmune responsePathological changesLeucocyte activationB cellsClinical relevanceSurfactant metabolismDisease pathologyInterferon responseFibrosisBlood vesselsPathological processesGene correlation network analysisPD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production
Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles R, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine 2018, 10 PMID: 30257954, PMCID: PMC6263177, DOI: 10.1126/scitranslmed.aar8356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBleomycinCD4-Positive T-LymphocytesCell ProliferationCollagen Type IDisease Models, AnimalFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisInterleukin-17MaleMiceMiddle AgedProgrammed Cell Death 1 ReceptorRNA, MessengerSarcoidosisSTAT3 Transcription FactorTh17 CellsTransforming Growth Factor beta1Up-RegulationConceptsIdiopathic pulmonary fibrosisPD-1Pulmonary fibrosisT cellsCollagen-1 productionPD-1 pathway blockadeCell death ligand 1T helper 17 (Th17) cellsPD-1 regulationIL-17A expressionProgressive inflammatory diseaseDeath ligand 1Helper 17 cellsT cell subsetsCell death 1Limited therapeutic optionsTGF-β1 productionLung disease pathophysiologyHuman lung fibroblastsPredominant CD4Bleomycin administrationIL-17ADeath-1Therapeutic optionsCell subsets
2017
Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis
Hawkins C, Shaginurova G, Shelton DA, Herazo-Maya JD, Oswald-Richter KA, Rotsinger JE, Young A, Celada LJ, Kaminski N, Sevin C, Drake WP. Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis. Journal Of Immunology Research 2017, 2017: 3642832. PMID: 29234685, PMCID: PMC5695030, DOI: 10.1155/2017/3642832.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedApoptosisCD4-Positive T-LymphocytesCell ProliferationCells, CulturedClonal AnergyCytokinesDisease ProgressionFemaleGene Expression RegulationHumansLymphocyte ActivationMaleMiddle AgedProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-Cell, alpha-betaSarcoidosis, PulmonaryTh1 CellsYoung AdultConceptsT cell exhaustionTh1 cytokine expressionPD-1 expressionCell exhaustionCytokine expressionT cellsHealthy controlsInhibitory cell surface receptorsT cell immune functionTh1 immune responseChronic antigenic stimulationCell immune functionProliferative capacityT cell functionSarcoidosis subjectsSystemic CD4Pulmonary sarcoidosisDisease resolutionProgressive diseaseClinical resolutionCytokine productionAntigenic stimulationDisease progressionImmune responseCD4Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12
Tan J, Tedrow JR, Nouraie M, Dutta JA, Miller DT, Li X, Yu S, Chu Y, Juan-Guardela B, Kaminski N, Ramani K, Biswas PS, Zhang Y, Kass DJ. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12. The Journal Of Immunology 2017, 198: 2269-2285. PMID: 28179498, PMCID: PMC5337810, DOI: 10.4049/jimmunol.1600610.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF patientsLung injuryPulmonary fibrosisT cellsFibrotic lung injuryIPF lung fibroblastsExperimental lung injuryT-cell pathwayApoptosis-resistant fibroblastsMatrix-producing cellsChemoattractant CXCL12Exaggerated fibrosisIPF phenotypeCollagen-producing cellsTranscription factor Twist1Prosurvival phenotypeFibrosisTwist1 expressionIncreased expressionLung fibroblastsCXCL12Low expressionHigh expressionCell pathways
2014
Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity
Braun NA, Celada LJ, Herazo-Maya JD, Abraham S, Shaginurova G, Sevin CM, Grutters J, Culver DA, Dworski R, Sheller J, Massion PP, Polosukhin VV, Johnson JE, Kaminski N, Wilkes DS, Oswald-Richter KA, Drake WP. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 560-571. PMID: 25073001, PMCID: PMC4214083, DOI: 10.1164/rccm.201401-0188oc.Peer-Reviewed Original ResearchConceptsPD-1 pathway blockadeT cell proliferative capacityPeripheral blood mononuclear cellsPD-L1 expressionPD-1 pathwayBlood mononuclear cellsT cell functionPathway blockadePD-L1Clinical outcomesLung diseaseMononuclear cellsControl subjectsProliferative capacityT cellsImmunohistochemistry analysisPD-1/PD-L1 expressionControl peripheral blood mononuclear cellsHealthy control peripheral blood mononuclear cellsHealthy control lungsIdiopathic lung diseaseSpontaneous clinical resolutionChronic lung diseaseHealthy control subjectsEffective therapeutic interventions
2013
Peripheral Blood Mononuclear Cell Gene Expression Profiles Predict Poor Outcome in Idiopathic Pulmonary Fibrosis
Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma SF, Tseng GC, Feingold E, Juan-Guardela BM, Richards TJ, Lussier Y, Huang Y, Vij R, Lindell KO, Xue J, Gibson KF, Shapiro SD, Garcia JG, Kaminski N. Peripheral Blood Mononuclear Cell Gene Expression Profiles Predict Poor Outcome in Idiopathic Pulmonary Fibrosis. Science Translational Medicine 2013, 5: 205ra136. PMID: 24089408, PMCID: PMC4175518, DOI: 10.1126/scitranslmed.3005964.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCD28 AntigensCD4 AntigensCluster AnalysisCohort StudiesGene Expression ProfilingHumansIdiopathic Pulmonary FibrosisLeukocytes, MononuclearOligonucleotide Array Sequence AnalysisReproducibility of ResultsReverse Transcriptase Polymerase Chain ReactionSignal TransductionTreatment OutcomeConceptsTransplant-free survivalIdiopathic pulmonary fibrosisPeripheral blood mononuclear cell gene expression profilesReplication cohortCell gene expression profilesPoor outcomePulmonary fibrosisQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionProportional hazards modelTranscription-polymerase chain reactionGene expression profilesPotential cellular sourcesT cell activationIPF patientsLung transplantationMicroarray cohortPatient ageOutcome biomarkerPatient groupVital capacityPolymerase chain reactionT cellsDiscovery cohortITK expressionOral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study
Drake WP, Oswald-Richter K, Richmond BW, Isom J, Burke VE, Algood H, Braun N, Taylor T, Pandit KV, Aboud C, Yu C, Kaminski N, Boyd AS, King LE. Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study. JAMA Dermatology 2013, 149: 1040-1049. PMID: 23863960, PMCID: PMC3927541, DOI: 10.1001/jamadermatol.2013.4646.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAnti-Bacterial AgentsAzithromycinCD4-Positive T-LymphocytesChronic DiseaseDrug Therapy, CombinationEthambutolFemaleFollow-Up StudiesHumansLevofloxacinMaleMiddle AgedOfloxacinRifampinSarcoidosisSeverity of Illness IndexSingle-Blind MethodSkin DiseasesTranscriptomeTreatment OutcomeYoung AdultConceptsChronic cutaneous sarcoidosisCutaneous sarcoidosis lesionsAntimycobacterial therapyLesion diameterCutaneous sarcoidosisSarcoidosis lesionsDisease severityPlacebo-controlled studyPlacebo-treated groupCompletion of therapyT cell functionChronic granulomatous diseaseT cell receptor stimulationSignificant reductionConcomitant levofloxacinPlacebo regimenRifampin regimenSingle-MaskedPlacebo groupTreat analysisDermatology centersTherapeutic optionsGranulomatous diseaseT cellsLesion severity
2012
Cytokine-Like Factor 1 Gene Expression Is Enriched in Idiopathic Pulmonary Fibrosis and Drives the Accumulation of CD4+ T Cells in Murine Lungs Evidence for an Antifibrotic Role in Bleomycin Injury
Kass DJ, Yu G, Loh KS, Savir A, Borczuk A, Kahloon R, Juan-Guardela B, Deiuliis G, Tedrow J, Choi J, Richards T, Kaminski N, Greenberg SM. Cytokine-Like Factor 1 Gene Expression Is Enriched in Idiopathic Pulmonary Fibrosis and Drives the Accumulation of CD4+ T Cells in Murine Lungs Evidence for an Antifibrotic Role in Bleomycin Injury. American Journal Of Pathology 2012, 180: 1963-1978. PMID: 22429962, PMCID: PMC3354590, DOI: 10.1016/j.ajpath.2012.01.010.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAnimalsBleomycinCD4-Positive T-LymphocytesCiliary Neurotrophic Factor Receptor alpha SubunitCollagenDrug InteractionsEpithelial CellsGene Expression ProfilingHumansIdiopathic Pulmonary FibrosisMacrophages, AlveolarMaleMicePulmonary AlveoliRatsRats, Sprague-DawleyReceptors, CytokineRecombinant ProteinsRNA, MessengerUp-RegulationConceptsIdiopathic pulmonary fibrosisType II alveolar epithelial cellsCytokine receptor-like factor 1Alveolar epithelial cellsPulmonary fibrosisCardiotrophin-like cytokineCiliary neurotrophic factor receptorIPF lungsT cellsEpithelial cellsPathogenesis of IPFAccumulation of CD4IL-6 family membersExperimental pulmonary fibrosisFatal lung diseaseNeurotrophic factor receptorAntifibrotic responsesIPF pathogenesisT helperPulmonary accumulationBleomycin injuryInterleukin-6 familyLung diseaseAntifibrotic roleCytokine interferon
2010
CD28 Down-Regulation on Circulating CD4 T-Cells Is Associated with Poor Prognoses of Patients with Idiopathic Pulmonary Fibrosis
Gilani SR, Vuga LJ, Lindell KO, Gibson KF, Xue J, Kaminski N, Valentine VG, Lindsay EK, George MP, Steele C, Duncan SR. CD28 Down-Regulation on Circulating CD4 T-Cells Is Associated with Poor Prognoses of Patients with Idiopathic Pulmonary Fibrosis. PLOS ONE 2010, 5: e8959. PMID: 20126467, PMCID: PMC2813297, DOI: 10.1371/journal.pone.0008959.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCD4 T cellsPro-inflammatory cytokinesIPF patientsT cellsPulmonary fibrosisClinical eventsManifestations of IPFPeripheral blood CD4 T cellsCirculating CD4 T cellsMajor adverse clinical eventsBlood CD4 T cellsRegulatory T-cell marker FOXP3Proliferative T cell responsesAdaptive immune activationConfidence interval (CI) 1.6Cytotoxic mediators perforinOne-year freedomMajor adverse eventsAdverse clinical eventsT cell responsesAntigen-driven proliferationAntigen-induced proliferationCytokine multiplex assayClinical deterioration
2007
Cellular and Humoral Autoreactivity in Idiopathic Pulmonary Fibrosis
Feghali-Bostwick CA, Tsai CG, Valentine VG, Kantrow S, Stoner MW, Pilewski JM, Gadgil A, George MP, Gibson KF, Choi AM, Kaminski N, Zhang Y, Duncan SR. Cellular and Humoral Autoreactivity in Idiopathic Pulmonary Fibrosis. The Journal Of Immunology 2007, 179: 2592-2599. PMID: 17675522, DOI: 10.4049/jimmunol.179.4.2592.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCD4 T cellsT cellsIPF patientsAutoantibody productionPulmonary fibrosisEffector functionsProliferative responseAutologous CD4 T cellsLung extractsPeripheral CD4 T lymphocytesPeripheral CD4 T cellsT cell clonal expansionAutoreactive immune processesAdaptive immune mechanismsCD4 T lymphocytesMHC class IIMore effective therapiesCell clonal expansionCycles of stimulationHumoral autoreactivityOligoclonal expansionPathologic responseIL-10Hilar lymph