Complement 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 hostsA 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 modelRNF34CellsHedgehog-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