2017
An 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
2015
A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion
Hedl M, Abraham C. A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion. Gut 2015, 65: 1799. PMID: 26215868, PMCID: PMC5106344, DOI: 10.1136/gutjnl-2014-308922.Peer-Reviewed Original ResearchConceptsCaspase-8 activationMonocyte-derived macrophagesAutocrine IL-1βIL-18 secretionHost-microbial interactionsCytokine secretionHuman monocyte-derived macrophagesHuman myeloid cellsMyeloid cellsCaspase-1Intestinal myeloid cellsPattern recognition receptorsOligomerisation domainIL-1βPrimary human myeloid cellsReal-time PCRFunctional consequencesTpl2NFκB signalingRecognition receptorsRNA expressionIntestinal immune homeostasisERKMyeloid-derived cellsJNKTwist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators
Zheng S, Hedl M, Abraham C. Twist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators. The Journal Of Immunology 2015, 195: 217-226. PMID: 26019273, PMCID: PMC4501480, DOI: 10.4049/jimmunol.1402808.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineActivating Transcription Factor 4Antibodies, NeutralizingCCAAT-Enhancer-Binding ProteinsCore Binding Factor Alpha 1 SubunitCore Binding Factor Alpha 2 SubunitGene Expression RegulationHumansInterleukin-10Macrophage ActivationMacrophagesNod2 Signaling Adaptor ProteinNuclear ProteinsPolycomb Repressive Complex 1Primary Cell CulturePromoter Regions, GeneticProtein BindingProto-Oncogene Proteins c-mafRepressor ProteinsRNA, Small InterferingSignal TransductionTranscription, GeneticTransforming Growth Factor betaTwist-Related Protein 1ConceptsChronic NOD2 stimulationCytokine downregulationNOD2 stimulationTwist2 expressionHuman macrophagesTGF-β dependentIntestinal immune homeostasisC-MafOligomerization domain 2IL-10Intestinal macrophagesImmune homeostasisTranscription factor 4PRR stimulationAcute stimulationDecreased expressionMacrophagesBMI1 expressionCytokinesNOD2StimulationTwist1DownregulationTranscriptional repressor Bmi1Factor 4
2014
Pattern 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 PKCSignalingNOD2 Regulates CXCR3-Dependent CD8+ T Cell Accumulation in Intestinal Tissues with Acute Injury
Wu X, Lahiri A, Haines GK, Flavell RA, Abraham C. NOD2 Regulates CXCR3-Dependent CD8+ T Cell Accumulation in Intestinal Tissues with Acute Injury. The Journal Of Immunology 2014, 192: 3409-3418. PMID: 24591373, PMCID: PMC4064676, DOI: 10.4049/jimmunol.1302436.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBone Marrow CellsCD3 ComplexCD8-Positive T-LymphocytesCell MovementCells, CulturedChemokine CXCL10Chemokine CXCL9ColitisDendritic CellsFlow CytometryGene ExpressionInterferon-gammaInterleukin-10Intestinal MucosaIntestinesMacrophagesMiceMice, Inbred C57BLMice, KnockoutModels, ImmunologicalNod2 Signaling Adaptor ProteinReceptors, CXCR3Reverse Transcriptase Polymerase Chain ReactionConceptsT cell accumulationT cell migrationT cell activationT cellsIntestinal injuryIntestinal tissueCell accumulationCell activationSmall intestinal lamina propriaIFN-γ neutralizationIntestinal T cellsT-cell depletionIntestinal immune homeostasisIL-10 productionT cell recruitmentHuman autoimmune diseasesIntestinal lamina propriaTreatment of miceIL-10 expressionIntestinal stromal cellsT cell outcomesCell migrationCXCR3 blockadeMAb administrationDendritic cells
2013
NF-κB1 Inhibits NOD2-Induced Cytokine Secretion through ATF3-Dependent Mechanisms
Zheng S, Abraham C. NF-κB1 Inhibits NOD2-Induced Cytokine Secretion through ATF3-Dependent Mechanisms. Molecular And Cellular Biology 2013, 33: 4857-4871. PMID: 24100018, PMCID: PMC3889551, DOI: 10.1128/mcb.00797-13.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsCells, CulturedCytokinesEpigenesis, GeneticGene Knockdown TechniquesHistonesHumansIleumMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-kappa B p50 SubunitNod1 Signaling Adaptor ProteinNod2 Signaling Adaptor ProteinPrimary Cell CulturePromoter Regions, GeneticProtein Processing, Post-TranslationalToll-Like Receptor 2Toll-Like Receptor 4Transcriptional ActivationConceptsChronic NOD2 stimulationIntestinal immune homeostasisCytokine secretionNOD2 stimulationNF-κB1Immune homeostasisHuman macrophagesNF-κB pathwayNF-κB1 expressionCytokine downregulationInhibitory pathwaysNOD2ATF3 expressionSecretionIntestinal environmentGene promoterCytokine gene promotersStimulationInhibitory histone modificationsATF3MacrophagesKnockdown conditionsCritical mechanismHomeostasisCytokines