2024
Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl mice
2021
Inflammasomes and Type 1 Diabetes
Pearson JA, Wong FS, Wen L. Inflammasomes and Type 1 Diabetes. Frontiers In Immunology 2021, 12: 686956. PMID: 34177937, PMCID: PMC8219953, DOI: 10.3389/fimmu.2021.686956.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaDiabetes Mellitus, Type 1Disease Models, AnimalDisease SusceptibilityHumansImmunity, InnateInflammasomesMicrobiotaSignal TransductionConceptsType 1 diabetesMultiprotein complexesEnhanced toleranceMicrobial ligandsIslet autoantibody developmentImmune responseGenetic associationMicrobial stimulationAvailable inhibitorsImportant modulatorType 1 diabetes susceptibilityPathwayDiabetes susceptibilityAutoimmune processMicrobiota compositionAutoantibody developmentMicrobiotaAnimal modelsInflammasomeActivationGenetic riskType 1DiabetesHumansRole
2020
TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model.
Sha S, Pearson JA, Peng J, Hu Y, Huang J, Xing Y, Zhang L, Zhu Y, Zhao H, Wong FS, Chen L, Wen L. TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model. Diabetes 2020, 70: 504-515. PMID: 33154070, PMCID: PMC7881860, DOI: 10.2337/db20-0373.Peer-Reviewed Original ResearchConceptsToll-like receptor 9B cellsNOD miceInterleukin-10IL-10-producing B cellsType 1 diabetes developmentAdaptive immune stimuliΒ-cell autoimmunityB-cell-specific deficiencyNovel therapeutic strategiesInnate immune moleculesB cell-specific deletionT1D developmentDiabetes protectionIL-10TLR9 deficiencyImmune toleranceDiabetes developmentReceptor 9T1D treatmentTLR9 pathwayImmune stimuliMouse modelTherapeutic strategiesMetalloproteinase-1Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse
Chen D, Thayer TC, Wen L, Wong FS. Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse. Methods In Molecular Biology 2020, 2128: 87-92. PMID: 32180187, PMCID: PMC8253669, DOI: 10.1007/978-1-0716-0385-7_6.Peer-Reviewed Original ResearchConceptsNonobese diabetic (NOD) miceType 1 diabetesDiabetic miceMouse modelHuman type 1 diabetesUnmanipulated NOD miceAutoimmune thyroid diseaseDifferent mouse modelsAutoimmune diathesesAutoimmune diabetesNOD miceSpontaneous diabetesAutoimmune typeThyroid diseaseRodent modelsDiabetesIncidence of diseaseNatural historyGenetic susceptibilityMiceNumerous transgenicKnockout modelsDiseaseAutoimmuneSialadenitis
2013
Role of IRAK-M in Alcohol Induced Liver Injury
Wang Y, Hu Y, Chao C, Yuksel M, Colle I, Flavell RA, Ma Y, Yan H, Wen L. Role of IRAK-M in Alcohol Induced Liver Injury. PLOS ONE 2013, 8: e57085. PMID: 23437317, PMCID: PMC3578822, DOI: 10.1371/journal.pone.0057085.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticCD8-Positive T-LymphocytesDisease Models, AnimalForkhead Transcription FactorsGenome-Wide Association StudyImmunophenotypingInterferon-gammaInterleukin-1 Receptor-Associated KinasesIntestinal MucosaIntestinesLiver Diseases, AlcoholicMetagenomeMiceMice, KnockoutPermeabilityPhagocytosisPhysical Chromosome MappingPolymorphism, Single NucleotideT-LymphocytesT-Lymphocytes, RegulatoryConceptsAbsence of IRAKAlcohol-induced liver injuryLiver injuryToll-like receptorsInnate immunityAlanine transaminaseAlcohol-induced liver injury modelsInterleukin receptor-associated kinaseAltered gut bacteriaHigher alanine transaminaseNumbers of IFNγWorse liver injuryAlcoholic liver injuryInduced liver injuryImmune cell infiltrationAdaptive immune responsesRole of IRAKLiver injury modelReceptor-associated kinaseGut permeabilityAcute insultB6 miceLiver damageCell infiltrationInjury model
2012
TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes
Dong B, Qi D, Yang L, Huang Y, Xiao X, Tai N, Wen L, Wong F. TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. AJP Heart And Circulatory Physiology 2012, 303: h732-h742. PMID: 22842069, PMCID: PMC3468457, DOI: 10.1152/ajpheart.00948.2011.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBlood GlucoseCell LineDiabetes Mellitus, Type 1Diabetic CardiomyopathiesDisease Models, AnimalFatty Acids, NonesterifiedJNK Mitogen-Activated Protein KinasesLipid MetabolismLipoprotein LipaseMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMyeloid Differentiation Factor 88MyocardiumMyocytes, CardiacOleic AcidP38 Mitogen-Activated Protein KinasesPhosphorylationRatsRNA InterferenceTime FactorsToll-Like Receptor 4TriglyceridesConceptsDiabetic heart diseaseType 1 diabetesHeart diseaseNOD animalsLipoprotein lipaseLipid accumulationNonobese diabetic (NOD) mouse modelLeft ventricular developed pressureCardiac fatty acid metabolismMyeloid differentiation primary response geneCardiac lipid accumulationControl nondiabetic miceGreater ejection fractionRole of TLR4Nonobese diabetic (NOD) miceOnset of diabetesVentricular developed pressureDevelopment of diabetesToll-like receptorsGreater fractional shorteningDiabetic mouse modelPlasma triglyceride levelsWild-type NODLower triglyceride accumulationCellular lipid accumulation
2011
IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice
Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L. IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clinical Immunology 2011, 139: 336-349. PMID: 21458378, DOI: 10.1016/j.clim.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenDendritic CellsDiabetes Mellitus, Type 1Disease Models, AnimalFemaleHLA-DQ AntigensHumansImmune ToleranceImmunophenotypingInsulin-Secreting CellsInterleukin-10Lymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred NODMice, SCIDMice, TransgenicSpecific Pathogen-Free OrganismsT-LymphocytesConceptsRIP-B7.1 miceAutoimmune diabetesIL-10IL-10-treated DCIL-12/23 p40T cell toleranceT cell proliferationDifferent animal modelsNew therapeutic interventionsSpontaneous diabetesRegulatory cellsDendritic cellsImmune toleranceCostimulatory moleculesIL-6IL-4T cellsAnimal modelsCell toleranceTherapeutic interventionsDiabetesCell proliferationT1D.MiceCells
2008
Developing a Novel Model System to Target Insulin‐Reactive CD8 T Cells
Scott G, Fishman S, Margalit A, Siew L, Chapman S, Wen L, Gross G, Wong F. Developing a Novel Model System to Target Insulin‐Reactive CD8 T Cells. Annals Of The New York Academy Of Sciences 2008, 1150: 54-58. PMID: 19120267, DOI: 10.1196/annals.1447.040.Peer-Reviewed Original Research
2003
Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans
Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans. International Immunology 2003, 15: 1035-1044. PMID: 12917255, DOI: 10.1093/intimm/dxg103.Peer-Reviewed Original ResearchConceptsCo-stimulatory molecules B7-1Incidence of diabetesTransgenic miceB7-1Autoimmune diabetesHLA-DQ8HLA-DR3T cellsBeta cellsBeta-cell toxin streptozotocinHLA class II associationsDQ8 transgenic micePresence of DR3HLA transgenic miceAntibody-mediated depletionPathogenesis of T1D.Class II associationsHLA class IIWhole-body irradiationPancreatic beta cellsNon-specific activationSpontaneous diabetesToxin streptozotocinDiabetogenic potentialSTZ treatment
2001
The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model
Wen L, Chen N, Tang J, Sherwin R, Wong F. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. Journal Of Clinical Investigation 2001, 107: 871-880. PMID: 11285306, PMCID: PMC199575, DOI: 10.1172/jci11708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, Type 1Disease Models, AnimalFemaleGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHLA-DR4 AntigenIncidenceInsulinMaleMiceMice, Inbred C57BLMice, TransgenicMicrosatellite RepeatsPancreasSialadenitisSpleenTh2 CellsTransgenesConceptsMHC class II moleculesSpontaneous diabetesClass II moleculesTransgenic miceT cellsHLA-DQ8Diabetogenic effectMouse MHC class II moleculesHLA-DR transgenic miceTh2-like immune responsesHuman type 1 diabetesAutoreactive T cellsDouble transgenic miceType 1 diabetesC57BL/6 transgenic miceTh2-like phenotypePancreatic beta cellsExpression of DR4DQ8 allelesDiabetes developmentCostimulatory moleculesHLA-DQImmune responseBeta cellsDiabetesType 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model
Abraham R, Wen L, Marietta E, David C. Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model. The Journal Of Immunology 2001, 166: 1370-1379. PMID: 11145722, DOI: 10.4049/jimmunol.166.2.1370.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceAnimalsAntibody SpecificityCells, CulturedCytokinesDiabetes Mellitus, Type 1Disease Models, AnimalEpitopes, T-LymphocyteGenes, MHC Class IIGenetic Predisposition to DiseaseGlutamate DecarboxylaseHLA-DQ AntigensHLA-DR3 AntigenHumansImmunophenotypingIslets of LangerhansIsoenzymesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataRatsT-Lymphocyte SubsetsConceptsGlutamic acid decarboxylaseGAD 65T cellsDQ8 miceMixed Th1/Th2 cytokine profileEndogenous MHC class IISpontaneous T-cell reactivityTh1/Th2 cytokine profileGlutamic acid decarboxylase 65Self-reactive responsesT cell reactivityTh2 cytokine profileAutoantigen glutamic acid decarboxylase 65Type 1 diabetesMHC class IIDiabetes-associated genesCytokine profileIslet autoantigensHLA-DR3Immune toleranceHLA-DQ6Cell reactivitySelf-AgImmune responseHLA alleles
2000
In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes
Wen L, Wong F, Tang J, Chen N, Altieri M, David C, Flavell R, Sherwin R. In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes. Journal Of Experimental Medicine 2000, 191: 97-104. PMID: 10620608, PMCID: PMC2195792, DOI: 10.1084/jem.191.1.97.Peer-Reviewed Original ResearchConceptsClass II moleculesMHC class II moleculesGlutamic acid decarboxylaseRat insulin promoterSpontaneous diabetesB7-1T cellsBeta cellsMouse MHC class II moleculesTransgenic miceHuman histocompatibility leukocyte antigenHuman type 1 diabetesMajor histocompatibility complex (MHC) class II moleculesCostimulatory molecules B7-1Human MHC class II moleculesVivo evidenceHistocompatibility leukocyte antigenDevelopment of diabetesType 1 diabetesMHC class IIC57BL/6 transgenic miceMurine MHC class IIPancreatic beta cellsVivo experimental evidenceDiabetogenic role
1997
Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse
Zekzer D, Wong F, Wen L, Altieri M, Gurlo T, von Grafenstein H, Sherwin R. Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse. Diabetes 1997, 46: 1124-1132. PMID: 9200646, DOI: 10.2337/diab.46.7.1124.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCattleCD4 AntigensCell Adhesion MoleculesClone CellsCytokinesDiabetes Mellitus, Type 2Disease Models, AnimalDose-Response Relationship, DrugFemaleFlow CytometryInsulinMiceMice, Inbred NODPolymerase Chain ReactionRatsReceptors, Antigen, T-Cell, alpha-betaRNASpecific Pathogen-Free OrganismsTh1 CellsConceptsNOD miceDiabetic splenocytesIslet supernatantAdoptive transferDiabetic miceCD4 T-cell clonesInhibition of diabetesInjection of splenocytesPancreatic lymph nodesNonobese diabetic (NOD) miceAnti-transforming growthT cell clonesTh1 cell linesT cell receptorNOD isletsNOD splenocytesSpontaneous diabetesInsulin therapyLymph nodesAntibody treatmentTh1 cellsProtective effectDiabetesB chain peptideSplenocytes
1996
Murine lupus in the absence of alpha beta T cells.
Peng SL, Madaio MP, Hughes DP, Crispe IN, Owen MJ, Wen L, Hayday AC, Craft J. Murine lupus in the absence of alpha beta T cells. The Journal Of Immunology 1996, 156: 4041-9. PMID: 8621947, DOI: 10.4049/jimmunol.156.10.4041.Peer-Reviewed Original ResearchConceptsAlpha beta T cellsT cell-dependent mechanismBeta T cellsCell-dependent mechanismT cellsMurine lupusHuman systemic lupus erythematosusLupus-prone MRL miceSystemic lupus erythematosusSystemic autoimmune diseaseLupus erythematosusAutoimmune diseasesImmune depositsMRL miceAlpha betaLupusDiseaseMiceCellsErythematosusHypergammaglobulinemiaAutoantibodiesCD4AutoimmunityKidney