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 oxidation
2023
New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events
Micevic G, Daniels A, Flavell R. New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events. British Journal Of Dermatology 2023, 189: 355-357. PMID: 37471669, PMCID: PMC10503525, DOI: 10.1093/bjd/ljad236.Peer-Reviewed Original ResearchConceptsCutaneous immune-related adverse eventsImmune-related adverse eventsSelf-reactive T cellsCheckpoint receptor PD-1PD-1 inhibitorsHalf of patientsImmune checkpoint blockadeAntitumor immune responseReceptor PD-1Adverse eventsCheckpoint blockadePD-1Immune toleranceCTLA-4T cellsImmune responseLandmark studiesMolecular mechanismsFunctional roleCritical functional rolePatientsBlockadeDermatologistsImportant cluesGasdermin D licenses MHCII induction to maintain food tolerance in small intestine
He K, Wan T, Wang D, Hu J, Zhou T, Tao W, Wei Z, Lu Q, Zhou R, Tian Z, Flavell R, Zhu S. Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell 2023, 186: 3033-3048.e20. PMID: 37327784, DOI: 10.1016/j.cell.2023.05.027.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsCleavage fragmentsSmall intestineCaspase-3/7 inhibitorRegulatory hubTolerance phenotypeN-terminal fragmentHost cellsDifferential cleavageCaspase-3/7Upper small intestineTranscription of CIITAGasdermin DEpithelial cellsMHCII deficiencyMHCII inductionDietary antigensTr1 cellsImmune toleranceProtective immunityFood toleranceForeign antigensMHCII moleculesMiceCells