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
2023
Assessing Obstetric Anal Sphincter Injuries
Zhao B, Li Y, Tang Y, Guo Y, Yang Y, Wen L, Dietz H. Assessing Obstetric Anal Sphincter Injuries. Journal Of Ultrasound In Medicine 2023, 42: 2031-2038. PMID: 36916688, DOI: 10.1002/jum.16221.Peer-Reviewed Original Research
2020
Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes
Huang J, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Guo K, Wong FS, Zhou Z, Wen L. Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa590. PMID: 32860693, PMCID: PMC7549925, DOI: 10.1210/clinem/dgaa590.Peer-Reviewed Original ResearchConceptsIgA-bound bacteriaType 1 diabetesHealthy control individualsIgA immune responseControl individualsIgA immunityAutoantibody titersIgA concentrationsImmune responseType 1 diabetes patientsΒ-cell autoimmunityLonger disease durationSerum IgA concentrationNovel therapeutic targetEnzyme-linked immunosorbentDisease durationIgA levelsDiabetes patientsDiabetes displayGut homeostasisBlood samplesOral cavityTherapeutic targetDiabetesHost immunityGut microbial metabolites alter IgA immunity in type 1 diabetes
Huang J, Pearson JA, Peng J, Hu Y, Sha S, Xing Y, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Wong F, Zhou Z, Wen L. Gut microbial metabolites alter IgA immunity in type 1 diabetes. JCI Insight 2020, 5 PMID: 32298241, PMCID: PMC7259536, DOI: 10.1172/jci.insight.135718.Peer-Reviewed Original ResearchConceptsType 1 diabetesGut microbiotaNOD miceImmune responseGerm-free NOD miceIgA immune responseIgA-mediated immunityHealthy control subjectsPotential therapeutic agentShort-chain fatty acid productionIgA immunityT1D preventionIgA responsesControl subjectsDecreased severityT1DTherapeutic agentsFunctional effectsMicrobiotaDiabetesPatientsUnderlying mechanismMiceImmunitySCFAMouse 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
2014
Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens
Kleffel S, Vergani A, Tezza S, Nasr M, Niewczas MA, Wong S, Bassi R, D’Addio F, Schatton T, Abdi R, Atkinson M, Sayegh MH, Wen L, Wasserfall CH, O’Connor K, Fiorina P. Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens. Diabetes 2014, 64: 158-171. PMID: 25187361, PMCID: PMC4274804, DOI: 10.2337/db13-1639.Peer-Reviewed Original ResearchConceptsIslet autoantigensB cellsT1D patientsInterleukin-10IL-10-producing B cellsHyperglycemic nonobese diabetic miceRegulatory B-cell responsesAutoreactive T cell responsesT cell-mediated responsesRole of BregsB-cell depletionRegulatory B cellsNonobese diabetic (NOD) miceNOD mouse modelT cell responsesB cell responsesType 1 diabetesB cell receptorAdoptive transferDiabetic miceAutoimmune diseasesHuman ILHyperglycemic miceMouse modelBregs
2013
TLR9 Deficiency Promotes CD73 Expression in T Cells and Diabetes Protection in Nonobese Diabetic Mice
Tai N, Wong FS, Wen L. TLR9 Deficiency Promotes CD73 Expression in T Cells and Diabetes Protection in Nonobese Diabetic Mice. The Journal Of Immunology 2013, 191: 2926-2937. PMID: 23956420, PMCID: PMC3788667, DOI: 10.4049/jimmunol.1300547.Peer-Reviewed Original ResearchConceptsNOD miceCD73 expressionT cellsTLR9 deficiencyDiabetes developmentImmune cellsAnti-inflammatory cytokine productionImproved β-cell functionImportant immune regulatory roleStrong immunosuppressive functionNonobese diabetic (NOD) miceIncidence of diabetesNOD mouse modelPeripheral lymphoid tissuesImmune regulatory roleType 1 diabetesΒ-cell functionNew therapeutic strategiesElevated frequencyNOD backgroundDiabetes protectionDiabetic miceImmunosuppressive functionProinflammatory cytokinesCytokine production
2011
Insulinoma-Released Exosomes or Microparticles Are Immunostimulatory and Can Activate Autoreactive T Cells Spontaneously Developed in Nonobese Diabetic Mice
Sheng H, Hassanali S, Nugent C, Wen L, Hamilton-Williams E, Dias P, Dai Y. Insulinoma-Released Exosomes or Microparticles Are Immunostimulatory and Can Activate Autoreactive T Cells Spontaneously Developed in Nonobese Diabetic Mice. The Journal Of Immunology 2011, 187: 1591-1600. PMID: 21734072, PMCID: PMC3150365, DOI: 10.4049/jimmunol.1100231.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCell Line, TumorCell-Derived MicroparticlesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1ExosomesFemaleHumansInsulinomaInsulin-Secreting CellsLymphocyte ActivationMaleMiceMice, Inbred NODMice, SCIDMyeloid Differentiation Factor 88Sex CharacteristicsTh1 CellsConceptsAutoreactive T cellsNOD miceAutoimmune targetT cellsCongenic miceNonobese diabetes-resistant miceHuman type 1 diabetesAg-specific immune responsesPrediabetic NOD micePancreatic lymph nodesNonobese diabetic (NOD) miceT cell responsesDiabetes-resistant miceAge-matched malesType 1 diabetesMyD88-dependent pathwayT cell proliferationResistant congenic miceInsulitis developmentPrediabetic NODInnate stimuliIslet destructionLymph nodesNOD femalesAutoimmune responseIL-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
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008, 455: 1109-1113. PMID: 18806780, PMCID: PMC2574766, DOI: 10.1038/nature07336.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1FemaleImmunity, InnateInterferon-gammaIntestinesIslets of LangerhansMaleMiceMice, Inbred NODMice, KnockoutMice, SCIDMolecular Sequence DataMyeloid Differentiation Factor 88PhylogenySpecific Pathogen-Free OrganismsTime FactorsConceptsType 1 diabetesNOD miceInnate immunityRapid innate immune responseDevelopment of diabetesNormal human gutInnate immune responseAdaptor protein MyD88Autoimmune diabetesTherapeutic optionsImmune responseNegative miceIntestinal microbiotaProtein MyD88DiabetesMiceGut microbesImmunityHuman gutMicrobial productsMyD88Influence predispositionIncidenceElevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease
WEN L, PEAKMAN M, MIELI-VERGANI G, VERGANI D. Elevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease. Clinical & Experimental Immunology 2008, 89: 78-82. PMID: 1385768, PMCID: PMC1554410, DOI: 10.1111/j.1365-2249.1992.tb06881.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAntigens, CDAutoimmune DiseasesChildCholangitis, SclerosingFemaleFlow CytometryFluorescent Antibody TechniqueHepatitis, ChronicHistocompatibility AntigensHLA-DR AntigensHumansLeukocyte Common AntigensLiver DiseasesMaleReceptors, Antigen, T-Cell, gamma-deltaReceptors, Interleukin-2T-LymphocytesConceptsPrimary sclerosing cholangitisGroup of patientsTCR gamma deltaT cellsAI-CAHLiver diseaseHLA-DRPeripheral bloodAutoimmune chronic active hepatitisAutoimmune chronic liver diseaseMemory cell marker CD45ROActivation markers HLA-DRΓδ T cell receptorAbsolute numberAutoimmune liver diseaseChronic active hepatitisChronic liver diseaseMarkers HLA-DRGamma delta T cell receptor (TCR) heterodimerIL-2 receptorT cell receptorT cell receptor heterodimerLevels of gammaActive hepatitisSclerosing cholangitisDifferences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
MA Y, PEAKMAN M, LOBO-YEO A, WEN L, LENZI M, GÄKEN J, FARZANEH F, MIELI-VERGANI G, BIANCHI F, VERGANI D. Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection. Clinical & Experimental Immunology 2008, 97: 94-99. PMID: 8033426, PMCID: PMC1534799, DOI: 10.1111/j.1365-2249.1994.tb06585.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibody SpecificityAutoantibodiesAutoantigensAutoimmune DiseasesB-LymphocytesChildChild, PreschoolCytochrome P-450 CYP2D6Cytochrome P-450 Enzyme SystemFemaleHepatitisHepatitis CHepatitis, ChronicHumansInfantMaleMiddle AgedMixed Function OxygenasesRecombinant Fusion ProteinsConceptsChronic hepatitis C virus (HCV) infectionHepatitis C virus infectionLKM-1 antibodiesAutoimmune hepatitisC virus infectionLKM-1HCV infectionVirus infectionCytochrome P4502D6Liver kidney microsomal antibodiesClassical autoimmune hepatitisKidney microsomal antibodyChronic HCV infectionLymphoblastoid B cell linesMicrosomal antibodiesPositive patientsLiver diseaseB cell linesHCVPatientsImmune recognitionMolecular mimicryRecombinant CYP2D6Western blotCYP2D6
2006
Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice
Gebe J, Unrath K, Falk B, Ito K, Wen L, Daniels T, Lernmark Å, Nepom G. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice. Clinical Immunology 2006, 121: 294-304. PMID: 16979383, PMCID: PMC1850983, DOI: 10.1016/j.clim.2006.08.002.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinNon-diabetic miceGlutamic acid decarboxylaseImmunodominant epitopesAcid decarboxylaseIslet-specific glucose-6-phosphatase catalytic subunit-related proteinHLA transgenic miceMean onset ageFibrillary acidic proteinAge-dependent lossIslet infiltratesOvert diabetesDiabetic miceFemale miceHistological evidenceMale miceDR4 miceYoung miceOnset ageProliferative responseDiabetic diseaseTransgenic miceImmunogenic epitopesAcidic proteinMice
2004
Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse
Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CA, Shlomchik MJ. Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse. Diabetes 2004, 53: 2581-2587. PMID: 15448087, DOI: 10.2337/diabetes.53.10.2581.Peer-Reviewed Original ResearchConceptsB cell-deficient miceAntigen-presenting functionType 1 diabetesB cellsNOD miceNormal NOD miceIncidence of diabetesDevelopment of diabetesT cell repertoireB cell repertoireAntigen presentationDiabetesAntibody productionMiceImmunoglobulin transgenesReduced abilityCell surfaceInsulitisAutoantibodiesIncidenceImmunoglobulinAntibodies
2003
Critical roles of CD30/CD30L interactions in murine autoimmune diabetes
CHAKRABARTY S, NAGATA M, YASUDA H, WEN L, NAKAYAMA M, CHOWDHURY S, YAMADA K, JIN Z, KOTANI R, MORIYAMA H, SHIMOZATO O, YAGITA H, YOKONO K. Critical roles of CD30/CD30L interactions in murine autoimmune diabetes. Clinical & Experimental Immunology 2003, 133: 318-325. PMID: 12930356, PMCID: PMC1808783, DOI: 10.1046/j.1365-2249.2003.02223.x.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalAutoimmune DiseasesCD30 LigandCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, ExperimentalFemaleIslets of LangerhansKi-1 AntigenMaleMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDT-LymphocytesT-Lymphocytes, CytotoxicConceptsCD30/CD30L interactionIslet-specific CD4NOD miceDevelopment of diabetesT cell linesAutoimmune diabetesDiabetic NOD miceSpontaneous autoimmune diabetesPancreatic lymph nodesYoung NOD miceNOD-SCID miceT cell proliferationCD30/CD30LTumor necrosis factor receptorWeeks of ageCell linesNecrosis factor receptorMurine autoimmuneIslet antigensSpontaneous diabetesAdoptive transferLymph nodesEffector phaseT cellsSpleen cells
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 cellsDiabetes
1994
T Cell Clones Generated from Patients with Type 1 Diabetes Using Interleukin-2 Proliferate to Human Islet Antigens
Peakman M, Wen L, McNab G, Watkins P, Tan K, Vergani D. T Cell Clones Generated from Patients with Type 1 Diabetes Using Interleukin-2 Proliferate to Human Islet Antigens. Autoimmunity 1994, 17: 31-39. PMID: 8025212, DOI: 10.3109/08916939409014656.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoantigensAutoimmune DiseasesCD4 AntigensCD8 AntigensChildChild, PreschoolClone CellsDiabetes Mellitus, Type 1FemaleHumansInterleukin-2Islets of LangerhansLymphocyte ActivationMaleReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaReceptors, Interleukin-2T-Lymphocyte SubsetsConceptsT cell clonesT lymphocytesIslet antigensControl subjectsAntigen specificityType 1Cell clonesT cell populationsPeripheral blood lymphocytesIL-2 receptorActivated T lymphocytesDose-dependent fashionPrediabetic periodLiver membrane preparationsPeripheral bloodAutologous APCIL-2Blood lymphocytesPatientsHuman isletsLymphocytesMembrane preparationsProliferation assaysPathogenesisAntigenAnalysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes
Wong S, Wen L, Hibberd M, Millward A, Demaine A. Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes. Autoimmunity 1994, 18: 77-83. PMID: 7999959, DOI: 10.3109/08916939409014682.Peer-Reviewed Original ResearchConceptsTCRBV gene usageGene usageSemi-quantitative polymerase chain reaction (PCR) techniqueType INormal healthy controlsBeta gene usagePeripheral T cellsT cell clonesPolymerase chain reaction techniqueClinical onsetHLA-DR3Chain reaction techniqueAutoimmune diseasesTCR repertoireHealthy controlsT cellsPatientsClinical diagnosisMarked activationSequential samplesSignificant differencesDiseaseDiagnosisDR4Cytometry
1990
T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis
Wen L, Peakman M, Lobo-Yeo A, Vergani D, Mowat A, Mieli-Vergani, McFarlane B. T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis. The Lancet 1990, 336: 1527-1530. PMID: 1979365, DOI: 10.1016/0140-6736(90)93306-a.Peer-Reviewed Original ResearchConceptsAutoimmune chronic active hepatitisChronic active hepatitisActive hepatitisPeripheral bloodT lymphocytesAutologous B lymphocytesLiver membrane antigensT cell clonesAsialoglycoprotein receptorActivated T lymphocytesLiver cell membraneSpecific autoantibodiesAutoimmune attackImmune attackHepatocyte damageHepatitisB lymphocytesLymphocytesBloodLipoprotein complexAutoantibodiesPatientsCell membraneAntigenClones
1987
Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies
Wen L, Hanvanich M, Werner‐Favre C, Brouwers N, Perrin L, Zubler R. Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies. European Journal Of Immunology 1987, 17: 887-892. PMID: 3297736, DOI: 10.1002/eji.1830170624.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsPeripheral blood B cellsHuman B cell responsesB cell frequenciesB cell responsesBlood B cellsB cell activationHuman T cellsHuman B cellsMalaria infectionPeripheral bloodBlood donorsT cellsEL4 thymoma cellsMacrophage supernatantsControl groupCell frequencyCell activationCell responsesSpecificity repertoireInfectious diseasesClonal levelCulture systemMean amount