2024
Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recovery
2023
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetIntegrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability
Habet V, Li N, Qi J, Peng G, Charkoftaki G, Vasiliou V, Sharma L, Pober J, Dela Cruz C, Yan X, Pierce R. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability. The Yale Journal Of Biology And Medicine 2023, 96: 23-42. PMID: 37009190, PMCID: PMC10052603, DOI: 10.59249/kfyz8002.Peer-Reviewed Original ResearchConceptsIntegrated stress responseProteomic analysisTranscriptional activityStress responseSingle-cell RNA sequencingCell RNA sequencingHuman pulmonary microvascular endothelial cellsMulti-omics approachCell type annotationRespiratory transport chainUnbiased proteomic analysisUpregulation of proteinsIngenuity Pathway AnalysisCardiopulmonary bypassCell clusteringProtective cellular responseFunctional cellular assaysDistinct cell populationsDEG analysisCellular phenotypesRNA sequencingPathway analysisTransport chainCellular responsesImmune cells
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacyCoronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challengesEpidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletion
2021
PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology.
Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 592-603. PMID: 33577398, PMCID: PMC8086043, DOI: 10.1165/rcmb.2020-0490oc.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBleomycinEpithelial CellsGene Expression RegulationHEK293 CellsHumansImmunity, InnateInflammasomesInfluenza A virusLungMiceMice, KnockoutMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinOrthomyxoviridae InfectionsPeroxisomesProtein AggregatesProtein BindingProtein KinasesPulmonary FibrosisSignal TransductionConceptsMAVS aggregationPINK1 deficiencyBimolecular fluorescence complementation analysisAntiviral innate immuneAppropriate cellular functionsKey molecular processesIntracellular signaling pathwaysInnate immune signalingComplementation analysisCellular functionsIntracellular perturbationsImmune signalingSignaling pathwaysPINK1Molecular processesMitochondria dysfunctionMAVSMAVS signalingMurine modelingSignalingFunctional significanceInnate immuneImportant roleRegulationNew role
2020
Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia
Gautam S, Stahl Y, Young GM, Howell R, Cohen AJ, Tsang DA, Martin T, Sharma L, Dela Cruz CS. Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2020, 319: l661-l669. PMID: 32783617, PMCID: PMC7642899, DOI: 10.1152/ajplung.00316.2020.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trapsAcute respiratory distress syndromeChronic obstructive pulmonary diseaseNeutrophil responseExtracellular trapsDysregulation of neutrophilsObstructive pulmonary diseaseRespiratory distress syndromeNeutrophil effector functionsEx vivo assaysBronchoalveolar neutrophilsSevere asthmaDistress syndromeLung neutrophilsPulmonary diseaseMurine pneumoniaMurine modelEffector functionsNeutrophil researchMouse lungCystic fibrosisMethodologic issuesMurine researchLungArray of diseasesDifferential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages
Chang D, Feng J, Liu H, Liu W, Sharma L, Dela Cruz CS. Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages. Innate Immunity 2020, 26: 618-626. PMID: 32762278, PMCID: PMC7556185, DOI: 10.1177/1753425920942582.Peer-Reviewed Original ResearchConceptsAkt pathwayEpithelial cellsCell typesKey cellular pathwaysLung epitheliumActivation of AktPhagocytic abilityMultiple cell typesAkt inhibitor MK2206Particular bacterial infectionsCellular pathwaysLung epithelial cellsMacrophage cell lineHost cellsBacterial infectionsRespiratory epithelial cellsCell proliferationType of infectionCell linesPathwayHost defenseDifferential rolesAktSC-79CellsChitotriosidase: a marker and modulator of lung disease
Chang D, Sharma L, Dela Cruz CS. Chitotriosidase: a marker and modulator of lung disease. European Respiratory Review 2020, 29: 190143. PMID: 32350087, PMCID: PMC9488994, DOI: 10.1183/16000617.0143-2019.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHarnessing Murine Microbiome Models to Study Human Lung Microbiome
Chang D, Sharma L, Dela Cruz CS. Harnessing Murine Microbiome Models to Study Human Lung Microbiome. CHEST Journal 2020, 157: 776-778. PMID: 32252931, PMCID: PMC7926993, DOI: 10.1016/j.chest.2019.12.011.Commentaries, Editorials and LettersEpidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China
Chang D, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA 2020, 323: 1092-1093. PMID: 32031568, PMCID: PMC7042871, DOI: 10.1001/jama.2020.1623.Peer-Reviewed Original ResearchMechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens
Sharma L, Feng J, Britto CJ, Dela Cruz CS. Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens. Frontiers In Immunology 2020, 11: 91. PMID: 32117248, PMCID: PMC7027138, DOI: 10.3389/fimmu.2020.00091.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBacterial lung infectionsImmune cellsBacterial clearanceRespiratory bacterial pathogensEpithelial cellsLung infectionSecretion of cytokinesEpithelial host defenseMuco-ciliary clearanceHuge economic burdenRespiratory epithelial cellsLung epithelial surfaceMajor healthcare challengeEpithelial immune mechanismsBacterial pathogensAntimicrobial peptide productionImmune mechanismsImmune protectionMucus productionEconomic burdenPathogen clearanceEpithelial immunityHost defenseClinical researchEpithelial resistance
2019
Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity
Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, Mack M, Schwartz MA, Dela Cruz CS, Palm NW, Jackson R, Flavell RA. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 2019, 573: 69-74. PMID: 31435009, PMCID: PMC6939392, DOI: 10.1038/s41586-019-1485-8.Peer-Reviewed Original ResearchConceptsInnate immune cellsImmune cellsInflammatory responseInnate immune systemCyclical hydrostatic pressurePulmonary inflammationImmune responseImmune systemInnate immunityBacterial infectionsIon channel Piezo1InflammationPhysiological fluctuationsImmunityPhysiological roleLocal microenvironmentCellsPiezo1Direct recognitionResponseAutoinflammationLungInfectionMice
2018
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammationRegulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae
Sharma L, Amick AK, Vasudevan S, Lee SW, Marion CR, Liu W, Brady V, Losier A, Bermejo SD, Britto CJ, Lee CG, Elias JA, Dela Cruz CS. Regulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae. The Journal Of Immunology 2018, 201: 615-626. PMID: 29891554, PMCID: PMC6291403, DOI: 10.4049/jimmunol.1701782.Peer-Reviewed Original ResearchConceptsLung infectionMouse modelRole of chitotriosidaseBronchoalveolar lavage fluidNumber of neutrophilsSimilar inflammatory responseRole of CHIT1Antibiotic therapyImproved survivalInflammatory changesLavage fluidInflammatory responseNeutrophil proteasesBacterial disseminationTrue chitinasesInfectionBeneficial effectsDetrimental roleAkt pathwayKlebsiella pneumoniaeAkt inhibitorCHIT1Chitinase-like proteinsMiceAkt activationInnate Immunity of the Lung: From Basic Mechanisms to Translational Medicine
Hartl D, Tirouvanziam R, Laval J, Greene CM, Habiel D, Sharma L, Yildirim AÖ, Dela Cruz CS, Hogaboam CM. Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine. Journal Of Innate Immunity 2018, 10: 487-501. PMID: 29439264, PMCID: PMC6089674, DOI: 10.1159/000487057.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRespiratory tractImmune systemInnate immunityHumoral host defense mechanismsPulmonary immune systemPulmonary innate immunityHost defense mechanismsInnate immune proteinsInnate armBroad armamentariumAirway compartmentImmune cellsChronic diseasesImmune proteinsTranslational medicineImmunityKey pathwaysTractRecent findingsDefense mechanismsAirwayLungArmamentariumDiseaseBiomarkers
2017
The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients
Kim HJ, Kim YS, Kim KH, Choi JP, Kim YK, Yun S, Sharma L, Dela Cruz CS, Lee JS, Oh YM, Lee SD, Lee SW. The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients. Experimental & Molecular Medicine 2017, 49: e316-e316. PMID: 28408748, PMCID: PMC5420800, DOI: 10.1038/emm.2017.7.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseCOPD groupLung tissueClinical characteristicsHealthy smokersNormal spirometryPresence of COPDExtracellular vesiclesHealthy smoker groupParticipants' clinical characteristicsSurgical lung tissueObstructive pulmonary diseaseChronic inflammatory diseaseSame mean ageRibosomal RNA gene sequencingRNA gene sequencingCOPD patientsSmoker groupImmune dysfunctionPulmonary diseaseSmoking statusMean ageNanometer-sized extracellular vesiclesLung microbiomeInflammatory diseasesChitin and Its Effects on Inflammatory and Immune Responses
Elieh Ali Komi D, Sharma L, Dela Cruz CS. Chitin and Its Effects on Inflammatory and Immune Responses. Clinical Reviews In Allergy & Immunology 2017, 54: 213-223. PMID: 28251581, PMCID: PMC5680136, DOI: 10.1007/s12016-017-8600-0.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune cellsCytokine productionImmune systemAdaptive immune cellsAlternative macrophage activationHost immune systemPathogen-associated molecular patternsPattern recognition receptorsTLR-2Mammalian immune systemImmunological aspectsAllergic responsesIntraperitoneal administrationLeukocyte recruitmentImmune responseAdaptive immunityMacrophage activationImmune recognitionRecognition receptorsTrue chitinasesNKR-P1Molecular patternsPotential targetMammalian chitinasesMammalian receptors