2024
IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.
Mullan C, Summer L, Lopez-Giraldez F, Tobiasova Z, Manes T, Yasothan S, Song G, Jane-Wit D, Saltzman W, Pober J. IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation. The Journal Of Immunology 2024, 213: 1338-1348. PMID: 39302113, PMCID: PMC11493510, DOI: 10.4049/jimmunol.2400331.Peer-Reviewed Original ResearchIL-15Surface expressionIL-1BIL-15 transcriptsEndothelial cellsCD8 T cell activationExpression of IL-15EC surface expressionIL-15 transpresentationComplement activationGraft endothelial cellsActivity of CTLT cell activationIL-15 mRNAEndothelial surface expressionAbsence of complement activationCultured human endothelial cellsIL-1-mediated activationIL-15RAProtein translationAllograft rejectionRNA polymerase II-mediated transcriptionHuman endothelial cellsSuppression of protein translation
2023
Transendothelial Migration of Human B Cells: Chemokine versus Antigen.
Wang V, Pober J, Manes T. Transendothelial Migration of Human B Cells: Chemokine versus Antigen. The Journal Of Immunology 2023, 211: 923-931. PMID: 37530585, PMCID: PMC10529164, DOI: 10.4049/jimmunol.2200887.Peer-Reviewed Original ResearchConceptsB cellsLeukocyte cell adhesion moleculeTransendothelial migrationEndothelial cellsCell adhesion moleculeAdhesion moleculesPeripheral blood CD19B cell subsetsMemory B cellsInnate immune propertiesSites of inflammationMicrovascular endothelial cellsHuman microvascular endothelial cellsHuman B cellsBlood CD19Peripheral bloodCell subsetsVenular flowT cellsICAM-1VCAM-1Immune propertiesSyk activationChemokinesExpression of genesA ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells
Li X, Jiang Q, Song G, Barkestani M, Wang Q, Wang S, Fan M, Fang C, Jiang B, Johnson J, Geirsson A, Tellides G, Pober J, Jane-wit D. A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature Communications 2023, 14: 3002. PMID: 37225719, PMCID: PMC10209169, DOI: 10.1038/s41467-023-38684-2.Peer-Reviewed Original ResearchConceptsEndothelial cellsInflammasome activityMembrane attack complexCaspase-1Potential therapeutic targetChronic rejectionComplement membrane attack complexTissue inflammationNLRP3 inflammasomeTissue injuryMouse modelTherapeutic targetDependent mannerInflammationAttack complexInflammasomeHuman tissuesFlightless IInhibitory associationsSkin modelRNF34CellsSingle-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis
Egozi A, Olaloye O, Werner L, Silva T, McCourt B, Pierce R, An X, Wang F, Chen K, Pober J, Shouval D, Itzkovitz S, Konnikova L. Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis. PLOS Biology 2023, 21: e3002124. PMID: 37205711, PMCID: PMC10234541, DOI: 10.1371/journal.pbio.3002124.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingSingle-cell atlasEpithelial cellsCell identityRNA sequencingBulk transcriptomicsCellular dysregulationAberrant interactionsNeonatal small intestinePotential targetCellular changesBiomarker discoveryGastrointestinal complicationsPremature infantsProinflammatory macrophagesProinflammatory genesClonal expansionT cellsEndothelial cellsImmune interactionsIntestinal tissueCellsSmall intestineComprehensive viewNECHedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells
Jiang B, Wang S, Song G, Jiang Q, Fan M, Fang C, Li X, Soh C, Manes T, Cheru N, Qin L, Ren P, Jortner B, Wang Q, Quaranta E, Yoo P, Geirsson A, Davis R, Tellides G, Pober J, Jane-Wit D. Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells. Science Signaling 2023, 16: eabo3406. PMID: 36943921, PMCID: PMC10061549, DOI: 10.1126/scisignal.abo3406.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryChronic vascular inflammationT cellsNLRP3 inflammasomeVascular inflammationChronic inflammationEndothelial cellsIFN-γ responsesControl T cellsNLRP3 inflammasome activityT memory cellsAllograft vasculopathyVascular sequelaeHuman endothelial cellsCoronary arteryEffector responsesCell-autonomous roleInflammasome activityMouse modelInflammationPatient samplesVigorous recruitmentInflammasomePrimary human cellsImmune signaling
2022
Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications
Albert C, Bracaglia L, Koide A, DiRito J, Lysyy T, Harkins L, Edwards C, Richfield O, Grundler J, Zhou K, Denbaum E, Ketavarapu G, Hattori T, Perincheri S, Langford J, Feizi A, Haakinson D, Hosgood SA, Nicholson ML, Pober JS, Saltzman WM, Koide S, Tietjen GT. Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications. Nature Communications 2022, 13: 5998. PMID: 36220817, PMCID: PMC9553936, DOI: 10.1038/s41467-022-33490-8.Peer-Reviewed Original ResearchConceptsTargeted delivery applicationsTargeted nanoparticlesAntibody immobilizationAntigen-binding functionNanoparticlesNP surfaceDelivery applicationsRobust deliveryEndothelial cellsAmine couplingAntibody displayClinical translationIntracellular drug levelsVascular endothelial cellsCultured endothelial cellsNanomedicineDrug levelsVivo perfusionOrgan transplantsAdapterClinical settingHuman kidneyHuman settingImmobilizationEfficacyCostimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes
Manes TD, Wang V, Pober JS. Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes. Frontiers In Immunology 2022, 13: 1016361. PMID: 36275645, PMCID: PMC9582530, DOI: 10.3389/fimmu.2022.1016361.Peer-Reviewed Original ResearchConceptsT effector cellsT cellsTransendothelial migrationEndothelial cellsCheckpoint inhibitorsEffector cellsCytokine productionCytokine synthesisPeripheral blood T cell subpopulationsEffector memory T cellsEngagement of OX40Presentation of superantigensRegulatory T cellsMemory T cellsT cell subpopulationsT-cell typeT cell CD28Antigen-independent signalT cell activationT cell receptorHuman dermal microvascularCD8 effectorsT-regsHuman endothelial cellsActivated CD4Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs
Liburd ST, Shi AA, Pober JS, Tietjen GT. Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs. American Journal Of Transplantation 2022, 22: 1754-1759. PMID: 35373446, PMCID: PMC9651180, DOI: 10.1111/ajt.17050.Peer-Reviewed Original ResearchConceptsNormothermic machine perfusionEndothelial cellsGraft vasculaturePoor outcomePreservation injuryMachine perfusionProfound shortageOrgan assessmentTransplant therapeuticsDonor comorbiditiesAllograft organClinical useOrgansAttractive targetNanotherapeutic deliveryTherapeutic vehiclesCellsTherapeutic deliveryDeliveryComorbiditiesTransplantGraftInjuryPerfusionVasculature
2021
Mitochondrial fission in allograft endothelial cells: A novel actionable target
Mullan CW, Pober JS. Mitochondrial fission in allograft endothelial cells: A novel actionable target. American Journal Of Transplantation 2021, 22: 337-338. PMID: 34865296, DOI: 10.1111/ajt.16911.Commentaries, Editorials and LettersTumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption
Khan A, Ni W, Lopez‐Giraldez F, Kluger MS, Pober JS, Pierce RW. Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption. The FASEB Journal 2021, 35: e21627. PMID: 33948992, PMCID: PMC9026622, DOI: 10.1096/fj.202002783rr.Peer-Reviewed Original ResearchConceptsCapillary endothelial cellsHuman dermal microvascular endothelial cellsMicrovascular endothelial cellsEndothelial cellsTight junctionsCultured human microvascular endothelial cellsEC tight junctionsLoss of barrierCapillary leak syndromeCapillary barrier functionDermal microvascular endothelial cellsRhoB activationTight junction disruptionDisrupts tight junctionsHuman microvascular endothelial cellsExtent of TNFHuman capillary endothelial cellsLeak syndromeOverwhelming inflammationCapillary leakBarrier lossTJ disruptionJunction disruptionRhoB knockdownTNFZFYVE21 is a Mediator of Non-Canonical Hedgehog Signaling Activating NLRP3 Inflammasomes in a Pathologic Subset of CD4+PD-1hi T Cells
Jiang B, Fang C, Soh C, Li X, Geirsson A, Tellides G, Pober J, Jane-Wit D. ZFYVE21 is a Mediator of Non-Canonical Hedgehog Signaling Activating NLRP3 Inflammasomes in a Pathologic Subset of CD4+PD-1hi T Cells. The Journal Of Heart And Lung Transplantation 2021, 40: s136. DOI: 10.1016/j.healun.2021.01.422.Peer-Reviewed Original ResearchT cellsNLRP3 inflammasomeEndothelial cellsDelayed graft functionSubset of CD4Humanized mouse modelComplement-mediated injuryNLRP3 inflammasome activityHuman lymphoid cellsNon-canonical Hedgehog signallingNon-canonical hedgehogGraft functionPeripheral injuryMemory CD4Human endothelial cellsPD-1Injury showCellular immunityVascular injuryChemokine receptorsTissue injuryPrimary human endothelial cellsInflammasome activityMouse modelLymphoid cells
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisComplement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells
Xie CB, Jiang B, Qin L, Tellides G, Kirkiles-Smith NC, Jane-wit D, Pober JS. Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. Journal Of Clinical Investigation 2020, 130: 3437-3452. PMID: 32191642, PMCID: PMC7324183, DOI: 10.1172/jci135060.Peer-Reviewed Original ResearchConceptsIL-15/IL-15Rα complexesIL-1βHuman endothelial cellsMembrane attack complexEndothelial cellsAcute rejectionT cellsT cell-mediated acute rejectionCell-mediated acute rejectionComplement-mediated pathologiesIL-15Rα expressionGraft endothelial cellsHuman coronary artery graftsEffector memory CD4T cell infiltrationCoronary artery graftsIL-1 receptorActive IL-1βCultured human endothelial cellsNLRP3 inflammasome assemblyNoncanonical NF-κBArtery graftAlloreactive CD8Complement membrane attack complexMemory CD4An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis
Korde A, Ahangari F, Haslip M, Zhang X, Liu Q, Cohn L, Gomez JL, Chupp G, Pober JS, Gonzalez A, Takyar SS. An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis. Journal Of Allergy And Clinical Immunology 2020, 145: 550-562. PMID: 32035607, PMCID: PMC8440091, DOI: 10.1016/j.jaci.2019.10.031.Peer-Reviewed Original ResearchConceptsMiR-1 levelsAllergic airway inflammationChronic rhinosinusitisP-selectin levelsEndothelium-specific overexpressionLung endotheliumAirway eosinophiliaAirway inflammationAsthmatic patientsTissue eosinophiliaMiR-1House dust mite modelEndothelial cellsThymic stromal lymphopoietinNumber of hospitalizationsHuman lung endotheliumIL-13 stimulationCRS cohortQuantitative RT-PCRSputum eosinophiliaAirway obstructionAsthma modelAsthma phenotypesLentiviral vector deliveryMurine modelEx vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium
Lysyy T, Bracaglia LG, Qin L, Albert C, Pober JS, Tellides G, Saltzman WM, Tietjen GT. Ex vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium. Bioengineering & Translational Medicine 2020, 5: e10154. PMID: 32440561, PMCID: PMC7237142, DOI: 10.1002/btm2.10154.Peer-Reviewed Original ResearchVessel perfusion systemAnimal modelsPerfusion systemProcess of inflammationVessel segmentsSame human donorEffective clinical translationImmunodeficient miceUmbilical cordRodent modelsHuman donorsEndothelial cellsHuman vesselsBiologic relevanceBiologic replicatesClinical translationSubsequent studiesEfficacyCultured cellsModular chambersCell culturesVivoCellsQuantitative assayVessels
2019
Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells
Baltazar T, Merola J, Catarino C, Xie C, Kirkiles-Smith N, Lee V, Hotta S, Dai G, Xu X, Ferreira FC, Saltzman WM, Pober JS, Karande P. Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells. Tissue Engineering Part A 2019, 26: 227-238. PMID: 31672103, PMCID: PMC7476394, DOI: 10.1089/ten.tea.2019.0201.Peer-Reviewed Original ResearchConceptsSkin graftsHuman endothelial colony-forming cellsEndothelial cellsHuman endothelial cellsHuman skin graftsEndothelial colony-forming cellsPlacental pericytesGraft survivalCutaneous ulcersAllogeneic cellsHuman foreskin keratinocytesMouse microvesselsImmunodeficient miceHuman pericytesGraftColony-forming cellsVascular structuresWound bedForeskin keratinocytesEpidermal maturationPericytesHuman placental pericytesHuman keratinocytesKeratinocytesType IEndothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activationZFYVE21 is a Novel Complement-Induced Rab5 Effector Protein Mediating Cardiac Allograft Vasculopathy
Jane-Wit D, Fang C, Liu L, Qin L, Li G, Tellides G, Pober J. ZFYVE21 is a Novel Complement-Induced Rab5 Effector Protein Mediating Cardiac Allograft Vasculopathy. The Journal Of Heart And Lung Transplantation 2019, 38: s249. DOI: 10.1016/j.healun.2019.01.618.Peer-Reviewed Original ResearchCardiac allograft vasculopathyAllograft vasculopathyHumanized mouse modelMembrane attack complexNF-κB-inducing kinaseTransplant biopsiesMouse modelEC activationHuman coronary artery segmentsEndothelial cellsAntibody-mediated rejectionTransplant organ rejectionCoronary artery segmentsHuman lymphoid cellsVascular inflammationOrgan rejectionArtery segmentsPharmacologic alterationsVasculopathyLymphoid cellsNF-kBClinical relevance
2015
Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli
Chang WG, Fornoni A, Tietjen G, Mendez JJ, Niklason LE, Saltzman WM, Pober JS. Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. Tissue Engineering Part A 2015, 21: 2673-2679. PMID: 26414101, PMCID: PMC4652181, DOI: 10.1089/ten.tea.2015.0060.Peer-Reviewed Original ResearchComplement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes
Jane-wit D, Surovtseva YV, Qin L, Li G, Liu R, Clark P, Manes TD, Wang C, Kashgarian M, Kirkiles-Smith NC, Tellides G, Pober JS. Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 9686-9691. PMID: 26195760, PMCID: PMC4534258, DOI: 10.1073/pnas.1503535112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviral IAP Repeat-Containing 3 ProteinClathrinComplement Membrane Attack ComplexCoronary VesselsEndocytosisEndosomesEnzyme StabilityFlow CytometryHuman Umbilical Vein Endothelial CellsHumansHydrazonesInhibitor of Apoptosis ProteinsMice, SCIDNF-kappa BProtein BiosynthesisProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRab5 GTP-Binding ProteinsRNA, Small InterferingSecretory VesiclesSignal TransductionTNF Receptor-Associated Factor 3Ubiquitin-Protein LigasesConceptsNF-κB-inducing kinaseMembrane attack complexNoncanonical NF-κBGenome-wide siRNA screenComplement membrane attack complexNIK stabilizationDynamin-dependent mannerNoncanonical NF-κB signalingEndothelial cellsActive Rab5Attack complexSiRNA screenNF-κBAkt activationCytokine-mediated activationNF-κB signalingIκB kinaseSignalosomeRab5EndosomesKinaseAktInternalizationCoronary endothelial cellsActivation