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 roleVariantsMacrophagesATF6IRE1αArg284SignalingReticulumStressTransfectionPERK
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