Endothelial 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 activationComplement Membrane Attack Complexes Assemble NLRP3 Inflammasomes Triggering IL-1 Activation of IFN-γ–Primed Human Endothelium
Xie CB, Qin L, Li G, Fang C, Kirkiles-Smith NC, Tellides G, Pober JS, Jane-Wit D. Complement Membrane Attack Complexes Assemble NLRP3 Inflammasomes Triggering IL-1 Activation of IFN-γ–Primed Human Endothelium. Circulation Research 2019, 124: 1747-1759. PMID: 31170059, PMCID: PMC6557295, DOI: 10.1161/circresaha.119.314845.Peer-Reviewed Original ResearchConceptsMembrane attack complexEndothelial cellsComplement membrane attack complexIL-1βNLRP3 inflammasomeEC immunogenicityComplement activationAntibody-mediated complement activationInflammasome assemblyComplement-mediated pathologiesRenal allograft biopsiesGraft endothelial cellsHuman coronary artery graftsLate allograft failureCoronary artery graftsT cell responsesImmune-mediated pathologyActivate endothelial cellsIL-1 receptorIL-1 synthesisIL-1β secretionNoncanonical NF-κB signalingNF-κB signalingAttack complexImmunodeficient mouse hosts