2020
Complement 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 CD4Complement Membrane Attack Complex New Roles, Mechanisms of Action, and Therapeutic Targets
Xie CB, Jane-Wit D, Pober JS. Complement Membrane Attack Complex New Roles, Mechanisms of Action, and Therapeutic Targets. American Journal Of Pathology 2020, 190: 1138-1150. PMID: 32194049, PMCID: PMC7280757, DOI: 10.1016/j.ajpath.2020.02.006.Peer-Reviewed Original ResearchConceptsMembrane attack complexMAC assemblyExpression of inhibitorMechanism of actionFacilitate secretionDependent transcriptionPlasma membraneIntracellular signalingComplement membrane attack complexAbsence of lysisSignalingRecent insightsBiophysical propertiesComplement-mediated diseasesAttack complexTherapeutic targetCell activationDisease pathogenesisAdaptive immunityNew roleIL-18IL-1βCytolytic effectorsProinflammatory effectsProinflammatory proteins
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 activationProgenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression
Merola J, Reschke M, Pierce RW, Qin L, Spindler S, Baltazar T, Manes TD, Lopez-Giraldez F, Li G, Bracaglia LG, Xie C, Kirkiles-Smith N, Saltzman WM, Tietjen GT, Tellides G, Pober JS. Progenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression. JCI Insight 2019, 4 PMID: 31527312, PMCID: PMC6824302, DOI: 10.1172/jci.insight.129739.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsBeta 2-MicroglobulinCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCRISPR-Cas SystemsDisease Models, AnimalEndothelial CellsEndothelial Progenitor CellsFemaleFetal BloodGene Knockout TechniquesGraft RejectionHealthy VolunteersHumansIsoantibodiesKiller Cells, NaturalLymphocyte ActivationMiceMicrovesselsNuclear ProteinsOrgan TransplantationPrimary Cell CultureTissue EngineeringTrans-ActivatorsConceptsDonor-specific antibodiesClass II transactivatorEndothelial cellsMHC expressionAllogeneic natural killer (NK) cellsT effector memory cellsEffector memory T cellsClass IClass II major histocompatibility complex moleculesEffector memory cellsMHC molecule expressionMemory T cellsNatural killer cellsAlloreactive cytotoxic T lymphocytesAllogeneic endothelial cellsMajor histocompatibility complex moleculesCytotoxic T lymphocytesClass I MHC moleculesHistocompatibility complex moleculesI MHC moleculesAllogeneic CD4Donor leukocytesHuman endothelial cellsGraft perfusionKiller cellsZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Fang C, Manes TD, Liu L, Liu K, Qin L, Li G, Tobiasova Z, Kirkiles-Smith NC, Patel M, Merola J, Fu W, Liu R, Xie C, Tietjen GT, Nigrovic PA, Tellides G, Pober JS, Jane-wit D. ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes. Nature Communications 2019, 10: 2247. PMID: 31113953, PMCID: PMC6529429, DOI: 10.1038/s41467-019-10041-2.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsCarrier ProteinsCell LineComplement Membrane Attack ComplexCoronary VesselsDisease Models, AnimalEndosomesFemaleGraft RejectionHuman Umbilical Vein Endothelial CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, SCIDNF-kappa BPhosphatidylinositol PhosphatesRab5 GTP-Binding ProteinsUbiquitin-Protein LigasesVasculitisConceptsNF-κB-inducing kinaseMembrane attack complexNon-canonical NF-κBNF-κBEC activationEndothelial cellsTransplant organ rejectionConnective tissue diseaseHumanized mouse modelAllograft vasculopathySynovial tissueTissue diseaseVascular inflammationOrgan rejectionPharmacologic alterationsMouse modelDependent mannerAttack complexProteasome-dependent degradationInduction
2018
Interferon-γ converts human microvascular pericytes into negative regulators of alloimmunity through induction of indoleamine 2,3-dioxygenase 1
Liu R, Merola J, Manes TD, Qin L, Tietjen GT, López-Giráldez F, Broecker V, Fang C, Xie C, Chen PM, Kirkiles-Smith NC, Jane-Wit D, Pober JS. Interferon-γ converts human microvascular pericytes into negative regulators of alloimmunity through induction of indoleamine 2,3-dioxygenase 1. JCI Insight 2018, 3: e97881. PMID: 29515027, PMCID: PMC5922286, DOI: 10.1172/jci.insight.97881.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsAntigen PresentationCell CommunicationCells, CulturedDisease Models, AnimalEndothelial CellsEndothelium, VascularFemaleGraft RejectionHealthy VolunteersHuman Umbilical Vein Endothelial CellsHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaIsoantigensMice, SCIDMicrovesselsPericytesPrimary Cell CultureRNA, Small InterferingSkinSkin TransplantationT-Lymphocytes, CytotoxicTransplantation ChimeraTransplantation, HomologousTryptophanConceptsInduction of indoleamineHuman pericytesEndothelial cellsAllograft rejectionTryptophan depletionT cellsAcute T cell-mediated rejectionT cell-mediated rejectionEffector memory T cellsDioxygenase 1Early acute rejectionCell-mediated rejectionSkin allograft rejectionAlloreactive T cellsHuman renal allograftsMemory T cellsRole of ECsContribution of pericytesAcute rejectionRenal allograftsImmunoregulatory effectsImmunosuppressive propertiesHuman allograftsMouse modelMicrovascular pericytes