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 lociReceptors
2014
A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8–induced IL-1
Hedl M, Abraham C. A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8–induced IL-1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 13451-13456. PMID: 25197060, PMCID: PMC4169936, DOI: 10.1073/pnas.1404178111.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineADAM ProteinsADAM17 ProteinCaspase 8Cells, CulturedGenetic Predisposition to DiseaseHumansInterleukin-1LigandsMacrophagesMitogen-Activated Protein KinasesMycobacteriumMyeloid CellsNF-kappa BNod2 Signaling Adaptor ProteinPhosphatidylinositol 3-KinasesPolymorphism, Single NucleotideReceptors, Pattern RecognitionReceptors, Tumor Necrosis Factor, Member 25Signal TransductionSolubilityTissue Inhibitor of Metalloproteinase-3Tumor Necrosis Factor Ligand Superfamily Member 15ConceptsMost risk lociCaspase-8-dependent pathwayCytokine secretionGain of functionIntestinal myeloid cellsInflammatory bowel diseaseRisk lociIL-1 secretionTNFSF15 expressionPI3KPRR responsesBowel diseaseSignalingCytokine productionImmune homeostasisInflammatory diseasesHuman macrophagesIL-1Myeloid cellsAltered functionCytokinesTNFSF15MacrophagesSecretionDiseaseActivation 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 expressionPattern Recognition Receptor Signaling in Human Dendritic Cells is Enhanced by ICOS Ligand and Modulated by the Crohn’s Disease ICOSLG Risk Allele
Hedl M, Lahiri A, Ning K, Cho JH, Abraham C. Pattern Recognition Receptor Signaling in Human Dendritic Cells is Enhanced by ICOS Ligand and Modulated by the Crohn’s Disease ICOSLG Risk Allele. Immunity 2014, 40: 734-746. PMID: 24837102, PMCID: PMC4157904, DOI: 10.1016/j.immuni.2014.04.011.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCrohn DiseaseDendritic CellsEnzyme ActivationGTP-Binding ProteinsHL-60 CellsHumansInducible T-Cell Co-Stimulator LigandInducible T-Cell Co-Stimulator ProteinJNK Mitogen-Activated Protein KinasesMacrophagesNeoplasm ProteinsNF-kappa BNod2 Signaling Adaptor ProteinPhosphorylationPolymorphism, Single NucleotideProtein Kinase CReceptors for Activated C KinaseReceptors, Cell SurfaceReceptors, Pattern RecognitionRNA InterferenceRNA, Small InterferingSignal TransductionConceptsMonocyte-derived dendritic cellsInflammatory bowel diseaseCytokine secretionDendritic cellsImmune homeostasisICOS ligandHuman monocyte-derived dendritic cellsPattern recognition receptor signalingRisk allelesIntestinal immune homeostasisCrohn's disease phenotypeHuman dendritic cellsCostimulatory molecule ICOSOligomerization domain 2NF-κB activationDisease phenotypePattern recognition receptorsICOSL expressionBowel diseaseReceptor signalingRisk carriersSecretionHomeostasisKinases PKCSignaling