2024
A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance
Mertens R, Misra A, Xiao P, Baek S, Rone J, Mangani D, Sivanathan K, Arojojoye A, Awuah S, Lee I, Shi G, Petrova B, Brook J, Anderson A, Flavell R, Kanarek N, Hemberg M, Nowarski R. A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance. Immunity 2024, 57: 2077-2094.e12. PMID: 38906145, DOI: 10.1016/j.immuni.2024.06.001.Peer-Reviewed Original ResearchFatty acid oxidationStimulator of interferon genesMetabolic switchIL-18Immune toleranceIntestinal toleranceRelease of mitochondrial DNAActivation of stimulator of interferon genesSusceptibility to inflammationIL-18 stimulationIL-18 activityMitochondrial DNATolerogenic macrophagesChronic inflammationInterleukin-18Immune stateInflammatory challengeInflammatory responseMetabolic programmingSodium influxMacrophage-derivedImmune functionInterferon genesBistable switchAcid oxidationDHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Ren X, Liu Q, Zhou P, Zhou T, Wang D, Mei Q, Flavell R, Liu Z, Li M, Pan W, Zhu S. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. Nature Communications 2024, 15: 3080. PMID: 38594251, PMCID: PMC11004185, DOI: 10.1038/s41467-024-47235-2.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseIntestinal stem cellsIntestinal epithelial cellsEpithelial homeostasisSusceptibility to experimental colitisIncreased susceptibility to experimental colitisImpaired ISC functionStem cellsEpithelial barrier dysfunctionGenomic instabilityInflammatory bowel disease patientsPathogenesis of inflammatory bowel diseaseR-loop-mediated genome instabilityHallmarks of inflammatory bowel diseaseContinuous self-renewalBarrier dysfunctionExperimental colitisCrypt destructionEpithelial cellsInflammatory responseSelf-renewalBowel diseaseRisk factorsIntestinal epitheliumProtein levels
2014
Inflammasomes and intestinal homeostasis: regulating and connecting infection, inflammation and the microbiota
Gagliani N, Palm NW, de Zoete MR, Flavell RA. Inflammasomes and intestinal homeostasis: regulating and connecting infection, inflammation and the microbiota. International Immunology 2014, 26: 495-499. PMID: 24948595, PMCID: PMC4200027, DOI: 10.1093/intimm/dxu066.Peer-Reviewed Original ResearchConceptsIntestinal homeostasisInflammatory responsePathological tissue damageImmediate inflammatory responseConflicting studiesEnteric infectionsIntestinal microbiotaTissue damageInflammasome deficiencyInflammasomeStress-associated signalsInfectionPotential roleMicrobiotaHomeostasisCytosolic protein complexesRecent studies
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
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