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
Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis
Nechanitzky R, Nechanitzky D, Ramachandran P, Duncan G, Zheng C, Göbl C, Gill K, Haight J, Wakeham A, Snow B, Bradaschia-Correa V, Ganguly M, Lu Z, Saunders M, Flavell R, Mak T. Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis. Cell Death & Differentiation 2022, 30: 407-416. PMID: 36528755, PMCID: PMC9950465, DOI: 10.1038/s41418-022-01092-y.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisTh17 cellsMultiple sclerosisAutoimmune encephalomyelitisChAT expressionBrain-infiltrating immune cellsStrong TCR signalingCholinergic controlTherapeutic immunomodulationCholine acetyltransferaseImmune cellsCell pathogenicityDisease progressionChronic activationMouse modelTranscription factor Bhlhe40Novel targetAcetylcholineMRNA levelsPathogenic determinantsTCR signalingEncephalomyelitisCellsExpressionIL17Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis
Odell I, Steach H, Gauld S, Reinke-Breen L, Karman J, Carr T, Wetter J, Phillips L, Hinchcliff M, Flavell R. Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis. Science Immunology 2022, 7: eabq6691. PMID: 36490328, PMCID: PMC9840167, DOI: 10.1126/sciimmunol.abq6691.Peer-Reviewed Original ResearchConceptsLung fibrosisDendritic cellsImmune cellsDiffuse cutaneous systemic sclerosisPersistence of fibrosisCutaneous systemic sclerosisExtent of fibrosisType I interferonSystemic sclerosisAutoimmune diseasesAntifibrotic targetsTherapeutic administrationMouse modelI interferonLung samplesLung explantsFibrosisFibrotic tissueImmune signalsEpiregulin expressionPatient's skinExtracellular matrix productionGenetic deficiencyEpiregulinEGFR ligands
2014
Development and function of human innate immune cells in a humanized mouse model
Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA. Development and function of human innate immune cells in a humanized mouse model. Nature Biotechnology 2014, 32: 364-372. PMID: 24633240, PMCID: PMC4017589, DOI: 10.1038/nbt.2858.Peer-Reviewed Original Research
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