2023
Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataHedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsIL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4Transendothelial 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 genesSingle-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
Costimulators 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 CD4Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cells
2021
ZFYVE21 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 cellsComplement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells
Xie CB, Zhou J, Mackay S, Pober JS. Complement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells. American Journal Of Transplantation 2021, 21: 1902-1909. PMID: 33415805, PMCID: PMC8096653, DOI: 10.1111/ajt.16485.Peer-Reviewed Original Research
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 CD4
2014
Polarized Granzyme Release Is Required for Antigen-Driven Transendothelial Migration of Human Effector Memory CD4 T Cells
Manes TD, Pober JS. Polarized Granzyme Release Is Required for Antigen-Driven Transendothelial Migration of Human Effector Memory CD4 T Cells. The Journal Of Immunology 2014, 193: 5809-5815. PMID: 25367116, PMCID: PMC4258477, DOI: 10.4049/jimmunol.1401665.Peer-Reviewed Original ResearchConceptsEffector memory CD4 T cellsMemory CD4 T cellsCD4 T cellsT cellsTransendothelial migrationImmune synapse formationEndothelial cell monolayersInflammatory chemokinesMorphologic manifestationsGranzyme releaseSynapse formationTCR recognitionGranule dischargeDynein-driven transportChemokinesCell monolayersEarly eventsEndotheliumCytosolic granulesCellsMTOC reorientationProteolytic activityMicrotubule organizing centerMolecular requirementsGranule functionRapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2
Wang C, Qin L, Manes TD, Kirkiles-Smith NC, Tellides G, Pober JS. Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2. Journal Of Experimental Medicine 2014, 211: 395-404. PMID: 24516119, PMCID: PMC3949571, DOI: 10.1084/jem.20131125.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceBlotting, WesternCell AdhesionChromatin ImmunoprecipitationDNA PrimersEndothelial CellsFlow CytometryHumansImmunoblottingMechanistic Target of Rapamycin Complex 2Microscopy, FluorescenceMultiprotein ComplexesOncogene Protein v-aktReal-Time Polymerase Chain ReactionSirolimusT-LymphocytesTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1ConceptsVascular cell adhesion molecule-1VCAM-1 expressionEndothelial cellsActivation of ERK1/2Cell adhesion molecule-1TNF inductionInfiltration of leukocytesAdhesion molecule-1Inhibition of TNFPotential therapeutic targetAbility of rapamycinAbility of TNFTranscription factor IRF-1Hyperactivation of ERK1/2Inhibition of ERK1/2Venular flowT cellsEndothelial expressionInflamed tissuesVascular endotheliumMolecule-1Therapeutic targetRapamycin pretreatmentRenal glomeruliTNF
2013
Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesis
2011
Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells
Lebastchi AH, Khan SF, Qin L, Li W, Zhou J, Hibino N, Yi T, Rao DA, Pober JS, Tellides G. Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells. American Journal Of Transplantation 2011, 11: 2332-2341. PMID: 21812925, PMCID: PMC3203343, DOI: 10.1111/j.1600-6143.2011.03676.x.Peer-Reviewed Original ResearchConceptsEffector T cellsMemory T cellsNaïve T cellsT cellsIL-17Vascular cellsEffector memory T cellsAlloreactive memory T cellsGrowth factor-beta expressionMedial smooth muscle cellsHuman effector memory T cellsHuman coronary artery graftsIL-17 productionCoronary artery graftsIFN-γ productionAllogeneic endothelial cellsInterferon-gamma productionDevelopment of arteriosclerosisExpression of TGFRole of TGFSmooth muscle cellsImmunodeficient mouse hostsHuman T cellsIntimal compartmentMedial infiltration
2009
Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death
Choy JC, Pober JS. Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death. American Journal Of Transplantation 2009, 9: 2281-2291. PMID: 19663890, PMCID: PMC3505447, DOI: 10.1111/j.1600-6143.2009.02771.x.Peer-Reviewed Original ResearchConceptsHuman CD8 T cellsCD8 T cellsInducible NO synthaseT cellsActivated T cellsNitric oxideDeprivation-induced cell deathCell deathAllogeneic endothelial cellsT cell proliferationActivation-induced cell deathCytokine deprivationGeneration of NOT cell deathExogenous nitric oxideHuman T cellsNO augmentsAllogeneic responseS-nitrosylationNO synthaseProtective effectActivity of caspasesEndothelial cellsPharmacological inhibitorsDeathParacrine Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death (141.3)
Choy J, Pober J. Paracrine Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death (141.3). The Journal Of Immunology 2009, 182: 141.3-141.3. DOI: 10.4049/jimmunol.182.supp.141.3.Peer-Reviewed Original ResearchHuman CD8 T cellsCD8 T cellsT cellsActivated T cellsDeprivation-induced cell deathCell deathAllogeneic endothelial cellsT cell proliferationActivation-induced cell deathCytokine deprivationHuman T cellsProtein expression levelsNO augmentsAllogeneic responseS-nitrosylationProtective effectExogenous NOActivity of caspasesEndothelial cellsPharmacological inhibitorsDeathBcl-2Cell proliferationExpression levelsINOS
2003
Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease
Biedermann BC, Tsakiris DA, Gregor M, Pober JS, Gratwohl A. Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease. Bone Marrow Transplantation 2003, 32: 1077-1084. PMID: 14625579, DOI: 10.1038/sj.bmt.1704258.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCase-Control StudiesEndothelium, VascularFas Ligand ProteinGraft vs Host DiseaseHematopoietic Stem Cell TransplantationInterferon-gammaLymphocyte ActivationMembrane GlycoproteinsMolecular Diagnostic TechniquesRNA, MessengerSensitivity and SpecificitySurvivorsT-Lymphocytes, CytotoxicTransplantation, HomologousVon Willebrand FactorConceptsCytotoxic T lymphocytesEndothelial injuryT cell activationT cellsT lymphocytesHost diseaseSCT recipientsAllogeneic stem cell transplantationAllospecific cytotoxic T lymphocytesIFN-γ transcript levelsActive chronic GVHDEndothelial injury resultsCD8 T lymphocytesCD8 T cellsCD4 T cellsLong-term survivorsStem cell transplantationImportant effector cellsVon Willebrand factor plasma levelsAge-matched controlsVascular endothelial cellsChronic GVHDActive graftEffector cellsCell transplantation
2001
Human Endothelial Cell Presentation of Antigen and the Homing of Memory/Effector T Cells to Skin
POBER J, KLUGER M, SCHECHNER J. Human Endothelial Cell Presentation of Antigen and the Homing of Memory/Effector T Cells to Skin. Annals Of The New York Academy Of Sciences 2001, 941: 12-25. PMID: 11594565, DOI: 10.1111/j.1749-6632.2001.tb03706.x.Peer-Reviewed Original ResearchConceptsDermal endothelial cellsEffector T cell populationsMicrovascular endothelial cellsMemory T cellsT cell populationsT cellsDermal microvascular endothelial cellsEndothelial cellsE-selectinMemory/effector T cellsAntigen-specific inflammatory responsesHuman dermal endothelial cellsAdhesion moleculesEndothelial cell presentationEffector T cellsT cell recruitmentCutaneous immune reactionsClass II MHC moleculesHours of challengeAntigen-independent mannerVCAM-1 expressionCell populationsHuman dermal microvascular endothelial cellsCultured human endothelial cellsLeukocyte adhesion moleculesHUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1
Tereb D, Kirkiles-Smith N, Kim R, Wang Y, Rudic R, Schechner J, Lorber M, Bothwell A, Pober J, Tellides G. HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1. Transplantation 2001, 71: 1622-1630. PMID: 11435975, DOI: 10.1097/00007890-200106150-00023.Peer-Reviewed Original ResearchConceptsTumor necrosis factorHuman tumor necrosis factorArtery graftT cellsNecrosis factorPig coronary artery endothelial cellsHuman T-cell infiltrationVascular cell adhesion molecule-1Human peripheral blood mononuclearHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsHuman leukocytesEndothelial cellsMajor histocompatibility complex antigensCell adhesion molecule-1Graft endothelial cellsT-cell infiltratesBeige mouse modelCoronary artery endothelial cellsT cell infiltrationCoronary artery graftsBlood mononuclear cellsPeripheral blood mononuclearCoronary artery segmentsAdhesion molecule-1