2019
Progenitor-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