ZFYVE21 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 degradationInductionAlloantibody 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 pathogenesisHedgehog-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