2024
DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Ren X, Liu Q, Zhou P, Zhou T, Wang D, Mei Q, Flavell R, Liu Z, Li M, Pan W, Zhu S. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. Nature Communications 2024, 15: 3080. PMID: 38594251, PMCID: PMC11004185, DOI: 10.1038/s41467-024-47235-2.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseIntestinal stem cellsIntestinal epithelial cellsEpithelial homeostasisSusceptibility to experimental colitisIncreased susceptibility to experimental colitisImpaired ISC functionStem cellsEpithelial barrier dysfunctionGenomic instabilityInflammatory bowel disease patientsPathogenesis of inflammatory bowel diseaseR-loop-mediated genome instabilityHallmarks of inflammatory bowel diseaseContinuous self-renewalBarrier dysfunctionExperimental colitisCrypt destructionEpithelial cellsInflammatory responseSelf-renewalBowel diseaseRisk factorsIntestinal epitheliumProtein levelsAn Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice
Vossen C, Schmidt P, Wunderlich C, Mittenbühler M, Tapken C, Wienand P, Mirabella P, Cabot L, Schumacher A, Folz-Donahue K, Kukat C, Voigt I, Brüning J, Fenselau H, Wunderlich F. An Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice. Cells 2024, 13: 102. PMID: 38201306, PMCID: PMC10778503, DOI: 10.3390/cells13010102.Peer-Reviewed Original ResearchConceptsEnteroendocrine cellsIntestinal epithelial cellsEEC subtypesCrypt-villus axisSmall intestineTerminal villiMouse linesTriple transgenic miceLargest endocrine organIntersectional genetic approachMature enteroendocrine cellsCre recombinase miceGastrointestinal motilityCell type-specific targetingEndocrine organHormonal secretionGastrointestinal tractGlucose metabolismMature subtypesIntestinal stem cellsFunctional readaptationTransgene expressionStop cassetteIEC typesMice
2023
IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus
Ingle H, Makimaa H, Aggarwal S, Deng H, Foster L, Li Y, Kennedy E, Peterson S, Wilen C, Lee S, Suthar M, Baldridge M. IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus. Science Advances 2023, 9: eadi2562. PMID: 37703370, PMCID: PMC10499323, DOI: 10.1126/sciadv.adi2562.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsTuft cellsUninfected bystander cellsIFN-λ signalingSource of IFNImmune cellsIntestinal infectionsLeading causeViral gastroenteritisMNoVNorovirus pathogenesisCellular tropismPotent antiviralEpidemic viral gastroenteritisEpithelial cellsBystander cellsIFNNorovirusAntiviralsInfectionMurine norovirusIntercellular communicationPersistent strainsCellsVivoThe KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptorsGasdermin D licenses MHCII induction to maintain food tolerance in small intestine
He K, Wan T, Wang D, Hu J, Zhou T, Tao W, Wei Z, Lu Q, Zhou R, Tian Z, Flavell R, Zhu S. Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell 2023, 186: 3033-3048.e20. PMID: 37327784, DOI: 10.1016/j.cell.2023.05.027.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsCleavage fragmentsSmall intestineCaspase-3/7 inhibitorRegulatory hubTolerance phenotypeN-terminal fragmentHost cellsDifferential cleavageCaspase-3/7Upper small intestineTranscription of CIITAGasdermin DEpithelial cellsMHCII deficiencyMHCII inductionDietary antigensTr1 cellsImmune toleranceProtective immunityFood toleranceForeign antigensMHCII moleculesMiceCellsNLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice
Pearson J, Peng J, Huang J, Yu X, Tai N, Hu Y, Sha S, Flavell R, Zhao H, Wong F, Wen L. NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice. Frontiers In Immunology 2023, 14: 1147925. PMID: 36911699, PMCID: PMC9995752, DOI: 10.3389/fimmu.2023.1147925.Peer-Reviewed Original ResearchConceptsNlrp6-deficient miceType 1 diabetesNLRP6 deficiencyB cellsIL-10Non-obese diabetic (NOD) miceType 1 diabetes developmentRole of NLRP6Germ-free miceT cell proliferationB cell populationsIntestinal epithelial cellsBreg populationAutoimmune diabetesNOD miceCrohn's diseaseImmune toleranceDiabetes developmentDiabetic miceImmune cellsCD103Inflammasome proteinsImmune responseNLRP6Gut microbiota
2022
MHC class II-restricted-presentationMHC class II and DM molecules in chickens: different yet again
Wise D, Halabi S, Afrache H, Fakiola M, Parker A, Kaufman J. MHC class II-restricted-presentationMHC class II and DM molecules in chickens: different yet again. Molecular Immunology 2022, 150: 32-33. DOI: 10.1016/j.molimm.2022.05.108.Peer-Reviewed Original ResearchIntestinal epithelial cellsClass II moleculesKO cellsClass II A genesII moleculesClass I systemResistance to infectious diseasesRT-PCRBF2 genesWestern blottingDM locusClass II BI systemA geneChicken MHCGenetic associationTapasin geneCRISPR-Cas9DMB1Tissue section stainingGenesBLB2Closely-linkedB2-microglobulinGut tissueElevated 5‐hydroxytryptamine in COVID‐19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells
Hoque K, Hayashi M, Sheikh I, Banerjee A, Verma S, Leblanc N, Zeiss C, Ameen N, Chakraborty S. Elevated 5‐hydroxytryptamine in COVID‐19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells. The FASEB Journal 2022, 36: 10.1096/fasebj.2022.36.s1.0r556. PMCID: PMC9348250, DOI: 10.1096/fasebj.2022.36.s1.0r556.Peer-Reviewed Original ResearchEnterochromaffin cell hyperplasiaCalu-3 cellsSARS-CoV2 infectionCl(-) secretionIntestinal epitheliumCell hyperplasiaColonic tissueCalcium-activated Cl- currentsCOVID-19-associated diarrheaCalcium-activated chloride currentsHuman colorectal cancer tissuesANO1 protein expressionCOVID-19 therapyIntestinal Cl(-) secretionColorectal cancer tissuesUssing chamber experimentsANO1 currentsSeverity of symptomsCOVID-19Human terminal ileumHuman intestinal epitheliumIntestinal epithelial cellsWhole-cell currentsHuman colonic tissueCaco-2 cells
2021
Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease
Aggarwal N, Deerhake ME, DiPalma D, Shahi SK, Gaggioli MR, Mangalam AK, Shinohara ML. Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease. Cell Reports 2021, 37: 110170. PMID: 34965439, PMCID: PMC8759344, DOI: 10.1016/j.celrep.2021.110170.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsAcute GVHDHost diseaseMajor target organAcute graftBacteria AkkermansiaGastrointestinal pathologyMouse modelTarget organsFunction of osteopontinCD4Protective rolePotential biomarkersBeneficial effectsEpithelial cellsOPN isoformsMouse mutant modelsGVHDOsteopontinGraftCell deathDiseaseCellsMutant modelsAkkermansiaMitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology
Fujiwara H, Seike K, Brooks MD, Mathew AV, Kovalenko I, Pal A, Lee HJ, Peltier D, Kim S, Liu C, Oravecz-Wilson K, Li L, Sun Y, Byun J, Maeda Y, Wicha MS, Saunders TL, Rehemtulla A, Lyssiotis CA, Pennathur S, Reddy P. Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology. Nature Immunology 2021, 22: 1440-1451. PMID: 34686860, PMCID: PMC9351914, DOI: 10.1038/s41590-021-01048-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCase-Control StudiesCell CommunicationCells, CulturedColitisColonCytotoxicity, ImmunologicDisease Models, AnimalElectron Transport Complex IIEpithelial CellsFemaleGraft vs Host DiseaseHumansImmunity, MucosalIntestinal MucosaMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMitochondriaOxidative PhosphorylationSuccinic AcidT-LymphocytesConceptsGenetic experimental approachesCell-intrinsic featuresMetabolic flux studiesIntestinal epithelial cellsOxidative phosphorylationDisease severityT cell-mediated immunopathologyT cell-mediated colitisIntestinal epithelial cell damageProtein analysisSuccinate dehydrogenaseCell-mediated immunopathologyInflammatory bowel diseaseEpithelial cell damageHuman clinical samplesSuccinate levelsEpithelial cellsCritical roleSDHAHost diseaseBowel diseaseComplementary chemicalIntestinal diseaseT cellsMetabolic alterationsThe RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells
Wang Y, He K, Sheng B, Lei X, Tao W, Zhu X, Wei Z, Fu R, Wang A, Bai S, Zhang Z, Hong N, Ye C, Tian Y, Wang J, Li M, Zhang K, Li L, Yang H, Li HB, Flavell RA, Zhu S. The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2017432118. PMID: 33483420, PMCID: PMC7848544, DOI: 10.1073/pnas.2017432118.Peer-Reviewed Original ResearchConceptsRNA helicasesEssential biological processesPaneth cellsRNA helicase DHX15Antimicrobial protein expressionCell-specific functionsViral RNA sensorsRNA splicingHelicasesUlcerative colitis patientsCell-specific depletionDHX15Complete knockoutKey regulatorBiological processesIntestinal epithelial cellsLethality of miceVivo roleEnteric bacteriaRNA sensorsDextran sodiumColitis patientsLack of evidenceAntimicrobial responsesIntestinal inflammationCD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoV
2020
Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells
De La Cena K, Ho R, Amraei R, Woolf N, Tashjian J, Zhao Q, Richards S, Walker J, Huang J, Chitalia V, Rahimi N. Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells. American Journal Of Pathology 2020, 191: 157-167. PMID: 33129760, PMCID: PMC7788663, DOI: 10.1016/j.ajpath.2020.09.015.Peer-Reviewed Original ResearchConceptsCell cycleColorectal cancerCell cycle checkpoint arrestCell cycle inhibitor proteinsNovel tumor suppressor geneFull molecular mechanismsPutative tumor suppressorColon cancer cellsTumor suppressor geneG2/M phaseSporadic human colorectal cancerNormal intestinal epithelial cellsEpigenetic mechanismsCheckpoint arrestTMIGD1Inhibitor proteinNovel potential therapeutic targetIntestinal epithelial cellsMolecular mechanismsTumor suppressorPoor overall survivalSuppressor geneDevelopment of adenomasImmunoglobulin domainHuman colorectal cancerIntestinal Immune Homeostasis and Inflammatory Bowel Disease: A Perspective on Intracellular Response Mechanisms
Ranjan K. Intestinal Immune Homeostasis and Inflammatory Bowel Disease: A Perspective on Intracellular Response Mechanisms. Gastrointestinal Disorders 2020, 2: 24. DOI: 10.3390/gidisord2030024.Peer-Reviewed Original ResearchInflammatory bowel diseaseIntestinal epithelial cellsIntestinal immune homeostasisBowel diseaseImmune homeostasisMyeloid cellsPeripheral myeloid cellsChronic inflammatory conditionsGut-resident microbesUnfolded protein responseInflammatory conditionsIntestinal homeostasisSusceptible individualsHomeostatic environmentChronic stressIntracellular mechanismsOxidative stressEpithelial cellsEndoplasmic reticulumDiseaseHomeostasisResident microbesProtein responseCellsCellular stressCreatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function
Hall C, Lee J, Murphy E, Gerich M, Dran R, Glover L, Abdulla Z, Skelton M, Colgan S. Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. Gastroenterology 2020, 159: 984-998.e1. PMID: 32433978, PMCID: PMC7891846, DOI: 10.1053/j.gastro.2020.05.033.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBiopsyCase-Control StudiesCell LineColitis, UlcerativeColonCrohn DiseaseEnergy MetabolismEpithelial CellsFemaleGene Knockdown TechniquesHumansIntestinal MucosaMaleMembrane Transport ProteinsMiceMice, KnockoutMiddle AgedMitochondriaNerve Tissue ProteinsPlasma Membrane Neurotransmitter Transport ProteinsTight JunctionsConceptsInflammatory bowel diseaseIntestinal epithelial cellsColon tissuesTransepithelial electrical resistanceBarrier functionBowel diseaseTight junctionsSeverity of colitisEpithelial cellsInactive Crohn's diseaseIntestinal barrier dysfunctionMucosal biopsy specimensQRT-PCREpithelial integrityQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionIEC cell linesMucosal biopsiesUlcerative colitisCrohn's diseaseControl miceBarrier dysfunctionPolymerase chain reactionBiopsy specimensPatients
2019
1240 Increased Mucosal Innate Immune Activation in Hereditary Alpha Trytpasemia Subjects Is Predictive of Clinical Response to Tofacitanib Therapy
Glover S, Davis E, Shirley J, Konnikova L. 1240 Increased Mucosal Innate Immune Activation in Hereditary Alpha Trytpasemia Subjects Is Predictive of Clinical Response to Tofacitanib Therapy. The American Journal Of Gastroenterology 2019, 114: s691-s692. DOI: 10.14309/01.ajg.0000594488.99132.5d.Peer-Reviewed Original ResearchInnate immune activationIntestinal epithelial cellsImmune activationClinical responsePyroptosis levelsAbdominal painGI symptomsClonal mast cell diseaseLevels of pyroptosisSmall bowel biopsyMemory T cellsMcg/LTime of biopsyElevated serum tryptaseMast cell diseaseType of therapyJAK-STAT inhibitorBowel biopsyElevated tryptaseIEC pyroptosisAdalimumab therapyClinical symptomsHistologic evidenceMC activationTryptase levelsDual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains
Alfajaro M, Kim J, Barbé L, Cho E, Park J, Soliman M, Baek Y, Kang M, Kim S, Kim G, Park S, Le Pendu J, Cho K. Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains. Journal Of Virology 2019, 93: 10.1128/jvi.00941-19. PMID: 31243129, PMCID: PMC6714814, DOI: 10.1128/jvi.00941-19.Peer-Reviewed Original ResearchConceptsHisto-blood group antigensRotaTeq vaccineIntestinal epithelial cellsAlternative receptorSialic acidVaccine strainGroup antigensSevere rotavirus diseaseEpithelial cellsHuman intestinal epithelial cellsHuman small intestinal epithelial cellsNatural human infectionBearing strainsSmall intestinal epithelial cellsRotaTeq vaccine strainsMA-104 cellsTight junction proteinsGroup A rotavirusesRotavirus diseaseSevere diarrheaIntestinal enteroidsGroup ASurface sialic acidΑGal epitopesImportant causeEarly Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor
Alfajaro M, Cho E, Kim D, Kim J, Park J, Soliman M, Baek Y, Park C, Kang M, Park S, Cho K. Early Porcine Sapovirus Infection Disrupts Tight Junctions and Uses Occludin as a Coreceptor. Journal Of Virology 2019, 93: 10.1128/jvi.01773-18. PMID: 30463963, PMCID: PMC6364031, DOI: 10.1128/jvi.01773-18.Peer-Reviewed Original ResearchConceptsSevere acute gastroenteritisClaudin-1Acute gastroenteritisEntry factorsTight junctionsTJ proteinsLLC-PK cellsAdhesion molecule-1Common causative agentChinese hamster ovaryDisrupts tight junctionsIntestinal epithelial cellsTransepithelial electrical resistanceHisto-blood groupTJ protein occludinRole of TJsMolecule-1Functional coreceptorInfectionTerminal sialic acidAffordable drugsProtein occludinOccludinSpecific antibodiesEpithelial cells
2018
Tropism for tuft cells determines immune promotion of norovirus pathogenesis
Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C, Hykes BL, McAllaster MR, Balce DR, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang YT, MacDuff DA, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PM, Handley SA, van Lookeren Campagne M, Baldridge MT, Virgin HW. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 2018, 360: 204-208. PMID: 29650672, PMCID: PMC6039974, DOI: 10.1126/science.aar3799.Peer-Reviewed Original ResearchConceptsVirus infectionImmune promotionTuft cellsType 2 cytokinesEnteric virus infectionEnteric viral infectionsIntestinal epithelial cellsMNoV infectionNorovirus infectionCommensal microbiotaHost immunityViral infectionNorovirus pathogenesisRare typeImmune systemCellular tropismInfectionMouse intestineTarget cellsEpithelial cellsCell proliferationCytokinesTropismCD300lfCells
2017
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine
Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host & Microbe 2017, 22: 449-459.e4. PMID: 28966054, PMCID: PMC5679710, DOI: 10.1016/j.chom.2017.08.021.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsViral surface proteinsCellular tropismPersistent viral infectionNon-structural protein NS1Expression of NS1MNoV infectionSurface proteinsHost cytokinesAntiviral immunityHost determinantsInterferon lambdaViral infectionKey host determinantsViral non-structural proteinsCell tropismFecal sheddingNon-structural proteinsTropism determinantsEpithelial cellsGlobal causeInfectionTropismProtein NS1MNoV
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply