2023
IL-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 CD4
2022
Human neutrophil development and functionality are enabled in a humanized mouse model
Zheng Y, Sefik E, Astle J, Karatepe K, Öz HH, Solis AG, Jackson R, Luo HR, Bruscia EM, Halene S, Shan L, Flavell RA. Human neutrophil development and functionality are enabled in a humanized mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2121077119. PMID: 36269862, PMCID: PMC9618085, DOI: 10.1073/pnas.2121077119.Peer-Reviewed Original ResearchConceptsHumanized mouse modelMouse modelHuman immune systemHuman neutrophilsImmune systemFunctional human immune systemGranulocyte colony-stimulating factorUnique mouse modelColony-stimulating factorHuman G-CSFMISTRG miceG-CSF receptor geneBacterial burdenInfectious challengeG-CSFNeutrophilsMiceNeutrophil developmentReceptor geneDiseaseInflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2021
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophages