2023
ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samples
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
2020
Myeloid Cell Expression of LACC1 Is Required for Bacterial Clearance and Control of Intestinal Inflammation
Kang JW, Yan J, Ranjan K, Zhang X, Turner JR, Abraham C. Myeloid Cell Expression of LACC1 Is Required for Bacterial Clearance and Control of Intestinal Inflammation. Gastroenterology 2020, 159: 1051-1067. PMID: 32693188, PMCID: PMC8139320, DOI: 10.1053/j.gastro.2020.07.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesColitis, UlcerativeCytokinesDextran SulfateDisease Models, AnimalDNA-Binding ProteinsFemaleHost Microbial InteractionsHumansImmunity, MucosalIntestinal MucosaIntracellular Signaling Peptides and ProteinsMaleMiceMice, KnockoutMyeloid CellsPrimary Cell CultureSalmonella InfectionsSalmonella typhimuriumConceptsIntestinal lymphoid organsBurden of bacteriaDextran sodium sulfateWild-type miceLymphoid organsTh17 cytokinesIntestinal inflammationDendritic cellsMyeloid cellsT cellsTh2 cytokinesMesenteric lymph node dendritic cellsLymph node dendritic cellsMyeloid cell-derived cytokinesAdaptive T cell responsesT cell transfer colitisMyeloid-specific disruptionInflammatory bowel diseaseReactive oxygen speciesImmune-mediated diseasesT cell responsesT helper 1Cell-derived cytokinesT cell cytokinesBone marrow-derived macrophagesT Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation
Yan J, Pandey SP, Barnes BJ, Turner JR, Abraham C. T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation. Cell Reports 2020, 31: 107820. PMID: 32610123, PMCID: PMC7409536, DOI: 10.1016/j.celrep.2020.107820.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCell DifferentiationCell MovementColitisCytokinesGenetic Predisposition to DiseaseHumansInflammationInterferon Regulatory FactorsIntestinesLymph NodesMice, Inbred BALB CReceptors, Antigen, T-CellReceptors, ChemokineSignal TransductionT-LymphocytesUp-RegulationConceptsInflammatory outcomesTh17-associated transcription factorsMultiple immune-mediated diseasesPromotes Intestinal InflammationTh17-associated cytokinesAnti-inflammatory cytokinesImmune-mediated diseasesTh2-associated cytokinesChemokine-induced migrationExperimental colitisIntestinal inflammationUlcerative colitisHuman CD4IRF5 polymorphismsT cell signalingCytokinesCD4IRF5Th1Myeloid lineageGenetic carriersColitisCell migrationKey roleOutcomes
2019
LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes
Huang C, Hedl M, Ranjan K, Abraham C. LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes. Cell Reports 2019, 29: 4525-4539.e4. PMID: 31875558, PMCID: PMC7372507, DOI: 10.1016/j.celrep.2019.11.105.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 6EIF-2 KinaseEndoplasmic ReticulumEndoplasmic Reticulum StressEndoribonucleasesEnterococcus faecalisEscherichia coliGene Expression RegulationHeLa CellsHost-Pathogen InteractionsHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsMacrophagesNod2 Signaling Adaptor ProteinPhagocytosisPrimary Cell CultureProtein Serine-Threonine KinasesRiskSignal TransductionConceptsEndoplasmic reticulumER stressER stress sensorsHuman macrophagesInnate immune outcomesDisease risk variantsMultiple immune-mediated diseasesLaccase domainPattern recognition receptor NOD2HeLa cellsAntimicrobial pathwaysRisk variantsGenetic variantsLACC1Critical roleVariantsMacrophagesATF6IRE1αArg284SignalingReticulumStressTransfectionPERKIL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes
Sun R, Hedl M, Abraham C. IL23 induces IL23R recycling and amplifies innate receptor-induced signalling and cytokines in human macrophages, and the IBD-protective IL23R R381Q variant modulates these outcomes. Gut 2019, 69: 264. PMID: 31097538, PMCID: PMC6858485, DOI: 10.1136/gutjnl-2018-316830.Peer-Reviewed Original ResearchConceptsMonocyte-derived macrophagesHuman monocyte-derived macrophagesJanus kinase/signal transducerKinase/signal transducerDynamin-mediated endocytosisReceptor-induced signalingCell surface regulationR381Q variantIBD pathogenesisIntestinal myeloid cellsLate endosomesPattern recognition receptorsSignal transducerPathway membersDefines mechanismsReal-time PCRCell typesHeLa cellsSignalingKey playersRNA expressionHuman macrophagesPathwayWestern blotMyeloid 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
2016
Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases
Abraham C, Dulai PS, Vermeire S, Sandborn WJ. Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases. Gastroenterology 2016, 152: 374-388.e4. PMID: 27780712, PMCID: PMC5287922, DOI: 10.1053/j.gastro.2016.10.018.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCytokinesHumansInflammatory Bowel DiseasesInterleukin-23Janus KinasesLysophospholipidsMolecular Targeted TherapyOligonucleotidesPiperidinesProtein Kinase InhibitorsPyrimidinesPyrrolesSignal TransductionSmad7 ProteinSphingosineTh17 CellsTransforming Growth Factor betaUstekinumabConceptsInflammatory bowel diseaseTreatment of IBDBowel diseaseAnti-inflammatory mechanismsSeverity of colitisInflamed intestinal tissueCell pathwaysBiomarkers of responseImmune system pathwaysIBD pathogenesisInterleukin-23Proinflammatory cytokinesFuture trialsEffects of agentsClinical trialsCytokine pathwaysPatient featuresIntestinal tissueDevelopment of therapeuticsIL23System pathwaysPathway moleculesFunction variantsSelection of therapeuticsTrialsIRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation
Hedl M, Yan J, Abraham C. IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation. Cell Reports 2016, 16: 2442-2455. PMID: 27545875, PMCID: PMC5165654, DOI: 10.1016/j.celrep.2016.07.060.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineAdjuvants, ImmunologicAnimalsCell DifferentiationGene Expression RegulationGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitInterferon Regulatory FactorsInterleukin-1 Receptor-Associated KinasesIntracellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMice, KnockoutMutationNod2 Signaling Adaptor ProteinPrimary Cell CultureProtein BindingProto-Oncogene Proteins c-aktReceptor-Interacting Protein Serine-Threonine Kinase 2Signal TransductionTNF Receptor-Associated Factor 6ConceptsInterferon regulatory factor 5Akt2 activationPro-inflammatory cytokinesM1 macrophage polarizationGlycolytic pathway genesHuman macrophagesDisease-associated polymorphismsM1 polarizationMacrophage polarizationInflammatory M1 macrophage polarizationPathway genesProximal signalingOligomerization domainRegulatory factor 5Glycolytic pathwayEnhanced glycolysisGenetic variantsGlycolysisMetabolic outcomesIRF5 expressionM1 macrophagesCentral mediatorFactor 5CytokinesMacrophages
2015
MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation
Lahiri A, Hedl M, Abraham C. MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 10461-10466. PMID: 26240347, PMCID: PMC4547281, DOI: 10.1073/pnas.1501752112.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAutophagyCaspase 1CytokinesEnzyme ActivationGene Expression RegulationGenetic Predisposition to DiseaseGenotypeHomeostasisHumansInflammationInflammatory Bowel DiseasesLeukocytes, MononuclearLigandsMacrophagesMonocytesProtein Structure, TertiaryProtein Tyrosine Phosphatases, Non-ReceptorRisk FactorsRNA, Small InterferingSignal TransductionToll-Like ReceptorsConceptsPattern recognition receptorsCaspase-1 activationInflammatory bowel diseaseMTMR3 expressionReceptor-induced signalingHost pattern recognition receptorsCytokine secretionMultiple genetic lociPhosphatase domainMicrobial interactionsGenetic lociMTMR3Undefined roleAutophagyIL-1β secretionRecognition receptorsHuman macrophagesAutophagy levelEnhanced autophagyProtein 3Bowel diseaseCytokine productionRisk polymorphismsRisk allelesAltered functionA 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 4T Cell–Extrinsic CD18 Attenuates Antigen-Dependent CD4+ T Cell Activation In Vivo
Wu X, Lahiri A, Sarin R, Abraham C. T Cell–Extrinsic CD18 Attenuates Antigen-Dependent CD4+ T Cell Activation In Vivo. The Journal Of Immunology 2015, 194: 4122-4129. PMID: 25801431, PMCID: PMC4404034, DOI: 10.4049/jimmunol.1401328.Peer-Reviewed Original ResearchConceptsT cell activationCell proliferationAg-dependent T cell activationCell activationCell-extrinsic roleHematopoietic cellsEssential roleT cell proliferationCritical roleAdhesion moleculesΒ2 integrinsProliferationT cellsCellsActivationVivoActivation profilesAPCNaive T cellsSecondary lymphoid organsLeukocyte adhesion moleculesTraffickingRoleIntegrinsCD11b blockade
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 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
2012
Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Philip Schumm L, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D’Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, Silverberg M, Annese V, Hakonarson H, Brant S, Radford-Smith G, Mathew C, Rioux J, Schadt E, Daly M, Franke A, Parkes M, Vermeire S, Barrett J, Cho J. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012, 491: 119-124. PMID: 23128233, PMCID: PMC3491803, DOI: 10.1038/nature11582.Peer-Reviewed Original ResearchMeSH KeywordsColitis, UlcerativeCrohn DiseaseGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHaplotypesHost-Pathogen InteractionsHumansInflammatory Bowel DiseasesMycobacteriumMycobacterium InfectionsMycobacterium tuberculosisPhenotypePolymorphism, Single NucleotideReproducibility of Results