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 macrophages
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
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 functionCytokinesTNFSF15MacrophagesSecretionDisease