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
HIV-1 Vpu restricts Fc-mediated effector functions in vivo
Prévost J, Anand S, Rajashekar J, Zhu L, Richard J, Goyette G, Medjahed H, Gendron-Lepage G, Chen H, Chen Y, Horwitz J, Grunst M, Zolla-Pazner S, Haynes B, Burton D, Flavell R, Kirchhoff F, Hahn B, Smith A, Pazgier M, Nussenzweig M, Kumar P, Finzi A. HIV-1 Vpu restricts Fc-mediated effector functions in vivo. Cell Reports 2022, 41: 111624. PMID: 36351384, PMCID: PMC9703018, DOI: 10.1016/j.celrep.2022.111624.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityEffector functionsFc-mediated effector functionsHIV-1-infected cellsWild-type virusCorrelates of protectionRV144 vaccine trialHIV-1 infectionNon-neutralizing antibodiesFc effector functionsCell surface CD4Viral envelope glycoproteinsViral loadHumanized miceHumoral responseVaccine trialsCellular cytotoxicityHIV-1 VpuVpu expressionEnvelope glycoproteinInfected cellsNnAbsVirusVpuAdministrationPlatelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growth
2015
Niche-Dependent Growth of Malignant and Pre-Neoplastic Plasma Cells in Humanized Mice
Das R, Strowig T, Verma R, Koduru S, Hafemann A, Hopf S, Kocoglu M, Borsotti C, Zhang L, Branagan A, Eynon E, Manz M, Flavell R, Dhodapkar M. Niche-Dependent Growth of Malignant and Pre-Neoplastic Plasma Cells in Humanized Mice. Blood 2015, 126: 120. DOI: 10.1182/blood.v126.23.120.120.Peer-Reviewed Original ResearchBone marrow mononuclear cellsMultiple myelomaMarrow mononuclear cellsPlasma cellsPlasma cell tumorsInterleukin-6Tumor cellsAsymptomatic MMHumanized miceMononuclear cellsCell tumorsFlow cytometryPathogenesis of MMAsymptomatic multiple myelomaExtra-medullary sitesSetting of patientsHuman MM cellsInnate immune cellsPlasma cell disordersPlasma cell leukemiaPlasma cell cloneImmune-deficient miceHuman plasma cell tumorsInnate immune cell developmentSingle-cell mass cytometry
2010
Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung.
Willinger T, Rongvaux A, Takizawa H, Eynon E, Stevens S, Manz M, Flavell R. Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung. Blood 2010, 116: 3789. DOI: 10.1182/blood.v116.21.3789.3789.Peer-Reviewed Original ResearchHuman immune responsePulmonary alveolar proteinosisImmune responseHuman myeloid cellsKI miceCell reconstitutionMyeloid cellsEnhanced systemic inflammatory responseFunctional human immune systemGM-CSFStrong innate immune responseSystemic inflammatory responseInfluenza virus infectionIL-3Human immune cellsInnate immune responseNew mouse modelHuman alveolar macrophagesHuman immune systemGranulocyte-macrophage colonyPAP syndromeHumanized miceAlveolar proteinosisImmune cellsInflammatory response