2021
The E3 ubiquitin ligase RNF186 and RNF186 risk variants regulate innate receptor-induced outcomes
Ranjan K, Hedl M, Abraham C. The E3 ubiquitin ligase RNF186 and RNF186 risk variants regulate innate receptor-induced outcomes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2013500118. PMID: 34353900, PMCID: PMC8364215, DOI: 10.1073/pnas.2013500118.Peer-Reviewed Original ResearchMeSH KeywordsCytokinesHumansImmunity, InnateInflammatory Bowel DiseasesIntestinesMacrophagesMyeloid CellsNF-kappa BNod2 Signaling Adaptor ProteinPolymorphism, Single NucleotideReceptor-Interacting Protein Serine-Threonine Kinase 2Receptors, Pattern RecognitionToll-Like Receptor 2Toll-Like Receptor 4UbiquitinationUbiquitin-Protein LigasesConceptsPattern recognition receptorsE3 ubiquitin ligase activityStimulation of PRRsAntimicrobial reactive oxygen speciesMultiple pattern recognition receptorsLoss of functionLigase activityReactive nitrogen speciesComplex assemblyIntestinal myeloid cellsReactive oxygen speciesAutophagy pathwayDownstream signalingRNF186Bacterial clearanceRisk variantsRecognition receptorsHuman macrophagesOxygen speciesInnate immunityInflammatory bowel diseaseNitrogen speciesMicrobial clearanceSpeciesMyeloid cells
2017
Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes
Lahiri A, Hedl M, Yan J, Abraham C. Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes. Nature Communications 2017, 8: 15614. PMID: 28593945, PMCID: PMC5472760, DOI: 10.1038/ncomms15614.Peer-Reviewed Original ResearchMeSH KeywordsBacteriaCells, CulturedCrohn DiseaseCytokinesElectron Transport Complex IIExtracellular Signal-Regulated MAP KinasesHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMacrophagesNF-kappa BNod2 Signaling Adaptor ProteinP38 Mitogen-Activated Protein KinasesProteinsReactive Oxygen SpeciesReceptors, Pattern RecognitionRNA InterferenceRNA, Small InterferingSuccinate DehydrogenaseConceptsBacterial clearanceCytokine secretionDisease risk variantsReceptor-induced responsesMyeloid-derived cellsNOD2 stimulationRecognition receptorsHuman macrophagesSuccinate dehydrogenaseMtROS productionMitochondrial ROS productionROS productionOutcomesSDH activityMacrophagesSecretionFunctional consequencesClearanceLACC1PRRImportant contributorCellsDisease-associated lociReceptorsAn inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes
Yan J, Hedl M, Abraham C. An inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes. Journal Of Clinical Investigation 2017, 127: 2192-2205. PMID: 28436939, PMCID: PMC5451247, DOI: 10.1172/jci86282.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusCarrier ProteinsCase-Control StudiesCytokinesEnterococcus faecalisGene ExpressionGenetic Association StudiesGenetic Predisposition to DiseaseHEK293 CellsHeterozygoteHumansInflammatory Bowel DiseasesMacrophagesMAP Kinase Signaling SystemMyeloid CellsPolymorphism, Single NucleotidePrimary Cell CultureReceptors, Pattern RecognitionRisk FactorsStaphylococcus aureusConceptsInflammatory bowel diseasePattern recognition receptor signalingDisease risk variantsIntestinal immune homeostasisActivation of MAPKIBD risk lociINAVAPrimary human cellsBacterial clearanceIntestinal myeloid cellsRisk lociAutophagy pathwayProper regulationIntronic regionsHuman cellsImmune homeostasisReceptor signalingDownstream signalsPRR stimulationReactive oxygenIntestinal microbesNF-κB activationGenesNF-κB pathwayMAPK
2014
Activation of Pattern Recognition Receptors Up-Regulates Metallothioneins, Thereby Increasing Intracellular Accumulation of Zinc, Autophagy, and Bacterial Clearance by Macrophages
Lahiri A, Abraham C. Activation of Pattern Recognition Receptors Up-Regulates Metallothioneins, Thereby Increasing Intracellular Accumulation of Zinc, Autophagy, and Bacterial Clearance by Macrophages. Gastroenterology 2014, 147: 835-846. PMID: 24960189, PMCID: PMC4170054, DOI: 10.1053/j.gastro.2014.06.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAutophagyCaspase 1Cells, CulturedDNA-Binding ProteinsGene Expression RegulationHumansIntestinal MucosaIntestinesMacrophagesMetallothioneinMiceMice, Inbred C57BLMice, KnockoutNF-kappa BNod2 Signaling Adaptor ProteinRNA InterferenceTime FactorsToll-Like ReceptorsTranscription FactorsTransfectionZincConceptsMetal-regulatory transcription factor 1Human monocyte-derived macrophagesPattern recognition receptorsMonocyte-derived macrophagesIntracellular zincMyeloid-derived cellsSmall interfering RNAsBacterial clearanceGentamicin protection assaysInduction of autophagyTranscription factor 1Metallothionein geneMultiple genesInterfering RNAsIntestinal macrophagesSpecific proteinsOligomerization domain 2Domain 2Toll-like receptor 5AutophagyIntestinal lamina propria cellsContinuous stimulationSpecific pathogen-free facilityProtection assaysInduces expression