2023
Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study
Hu J, Ding J, Li X, Li J, Zheng T, Xie L, Li C, Tang Y, Guo K, Huang J, Liu S, Yan J, Peng W, Hou C, Wen L, Xu A, Zhou Z, Xiao Y. Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study. EClinicalMedicine 2023, 62: 102132. PMID: 37593224, PMCID: PMC10430172, DOI: 10.1016/j.eclinm.2023.102132.Peer-Reviewed Original ResearchAdult-onset T1DHealthy controlsGut microbiotaT1D patientsShort-chain fatty acid-producing bacteriaPopulation-based cross-sectional studyGut microbial alterationsRecent epidemiological dataType 1 diabetesCross-sectional studyT2D patientsIntestinal disturbancesDifferential diagnosisSerum metabolitesEpidemiological dataPatientsStudy subjectsT1DDiabetesSignificant differencesAcid-producing bacteriaMicrobiotaMicrobial profilesNational Key ResearchMicrobial alterations
2022
Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Yang ML, Connolly SE, Gee RJ, Lam TT, Kanyo J, Peng J, Guyer P, Syed F, Tse HM, Clarke SG, Clarke CF, James EA, Speake C, Evans-Molina C, Arvan P, Herold KC, Wen L, Mamula MJ. Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity. Diabetes 2022, 71: 1979-1993. PMID: 35730902, PMCID: PMC9450849, DOI: 10.2337/db21-0989.Peer-Reviewed Original ResearchConceptsType 1 diabetesNOD miceMurine type 1 diabetesHuman type 1 diabetesDecreased glucose-stimulated insulin secretionAnti-insulin autoimmunityPrediabetic NOD miceGlucose-stimulated insulin secretionOnset Type 1T cell responsesOnset of hyperglycemiaCirculation of patientsAutoreactive CD4Insulin ratioInsulin secretionDiabetesPancreatic isletsType 1Islet proteinsOxidative stressAutoimmunitySelect groupMiceCarbonyl modificationOnset
2021
Innate immunity in latent autoimmune diabetes in adults
Huang J, Pearson JA, Wong FS, Wen L, Zhou Z. Innate immunity in latent autoimmune diabetes in adults. Diabetes/Metabolism Research And Reviews 2021, 38: e3480. PMID: 34156143, PMCID: PMC8813511, DOI: 10.1002/dmrr.3480.Peer-Reviewed Original ResearchConceptsType 1 diabetesDendritic cellsImmune cellsT cellsInnate immunityPathogenesis of LADALatent autoimmune diabetesAdaptive immune cellsPancreas of patientsType 2 diabetesImmune-associated genesIslet β-cellsAutoimmune diabetesClinical featuresImmunological reasonsAutoimmune diseasesRat modelB cellsDiabetesΒ-cellsImmunityPotential rolePathogenesisLADADiseaseInflammasomes 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 ResearchConceptsType 1 diabetesMultiprotein complexesEnhanced toleranceMicrobial ligandsIslet autoantibody developmentImmune responseGenetic associationMicrobial stimulationAvailable inhibitorsImportant modulatorType 1 diabetes susceptibilityPathwayDiabetes susceptibilityAutoimmune processMicrobiota compositionAutoantibody developmentMicrobiotaAnimal modelsInflammasomeActivationGenetic riskType 1DiabetesHumansRole
2020
Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes.
Thayer TC, Davies J, Pearson JA, Hanna SJ, Wen L, Wong FS. Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes. Diabetes 2020, 70: 529-537. PMID: 33122391, PMCID: PMC8176215, DOI: 10.2337/db19-1050.Peer-Reviewed Original ResearchConceptsType 1 diabetesCD3/CD28T cellsAutoreactive cellsMHC-independent mechanismsNOD mouse modelT cell cytotoxicityΒ-cell destructionStromal cell regulationT cell receptor engagementPeripheral toleranceDiabetes developmentEffector functionsMouse modelAntigen sensitivityCD8Suppressive mechanismsStromal cellsType 1MHCReceptor engagementLNSCDiabetesIndependent mechanismsCD28Altered 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
2015
The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity
Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Reviews In Endocrine And Metabolic Disorders 2015, 16: 55-65. PMID: 25619480, PMCID: PMC4348024, DOI: 10.1007/s11154-015-9309-0.Peer-Reviewed Original ResearchConceptsGut microbiotaAutoimmune type 1 diabetesType 2 diabetes mellitusInsulin-resistant type 2 diabetesMajor public health concernAltered gut microbiotaDevelopment of T1DType 2 diabetesType 1 diabetesGut microbiota compositionPublic health concernDiabetes mellitusPersistent hyperglycemiaMetabolic disordersRodent modelsMicrobiota compositionType 1ObesityDiabetesHealth concernPotential mechanismsMicrobiotaT2DT1DDisease development
2014
Long term effect of gut microbiota transfer on diabetes development
Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. Journal Of Autoimmunity 2014, 53: 85-94. PMID: 24767831, PMCID: PMC4361177, DOI: 10.1016/j.jaut.2014.03.005.Peer-Reviewed Original ResearchConceptsNOD miceGut microbiotaWild-type NOD miceNon-obese diabetic (NOD) miceGut microbiomeMyD88-deficient miceMucosal immune systemOnset of diabetesCD8αβ T cellsType 1 diabetesGut microbiota transferWeeks of ageAutoimmune diabetesT1D developmentDiabetes developmentDiabetic miceMicrobiota transferT cellsLamina propriaLong-term effectsProbiotic treatmentImmune systemLarge intestineDiabetesMice
2012
Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes.
Wong F, Wen L. Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes. The Review Of Diabetic Studies 2012, 9: 289-304. PMID: 23804267, PMCID: PMC3740697, DOI: 10.1900/rds.2012.9.289.Peer-Reviewed Original ResearchConceptsInnate lymphocytesB cellsT cell targetingNatural killer cellsRecent clinical trialsPathogenesis of T1DType 1 diabetesType 1 diabetes therapyKiller cellsSpecific therapyClinical trialsT cellsDisease processDiabetes therapyMultifactorial diseaseCell pathwaysMultiple cell typesDiabetesT1DLymphocytesTherapyMonocytesDiseaseSuitable targetCell typesCorrection: The Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice
Hu C, Du W, Zhang X, Wong F, Wen L. Correction: The Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice. The Journal Of Immunology 2012, 188: 3552-3552. DOI: 10.4049/jimmunol.1290005.Peer-Reviewed Original ResearchThe Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice
Hu C, Du W, Zhang X, Wong FS, Wen L. The Role of Gr1+ Cells after Anti-CD20 Treatment in Type 1 Diabetes in Nonobese Diabetic Mice. The Journal Of Immunology 2012, 188: 294-301. PMID: 22140261, PMCID: PMC4361178, DOI: 10.4049/jimmunol.1101590.Peer-Reviewed Original ResearchConceptsType 1 diabetesT cell functionNOD miceCD8 T cell functionRegulatory T cell differentiationAnti-CD20 treatmentPancreatic islet autoimmunityB-cell depletionCell contact-dependent mannerNonobese diabetic (NOD) miceCell functionT cell differentiationContact-dependent mannerDiabetogenic CD4Islet autoimmunityNovel immunotherapiesIL-10Immune toleranceDiabetic miceAutoimmune diseasesCell depletionImmunoregulatory functionsDiabetesMiceDependent manner
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
2010
To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes
Wong F, Hu C, Xiang Y, Wen L. To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes. Current Opinion In Immunology 2010, 22: 723-731. PMID: 21050736, DOI: 10.1016/j.coi.2010.10.002.Peer-Reviewed Original ResearchImmunotargeting of insulin reactive CD8 T cells to prevent Diabetes
Scott G, Fishman S, Siew L, Margalit A, Chapman S, Chervonsky A, Wen L, Gross G, Wong F. Immunotargeting of insulin reactive CD8 T cells to prevent Diabetes. Journal Of Autoimmunity 2010, 35: 390-397. PMID: 20850948, DOI: 10.1016/j.jaut.2010.08.005.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsNOD miceAdoptive transferInsulin-reactive T cellsReactive CD8 T cellsInsulin-producing beta cellsPancreatic lymph nodesYoung NOD miceOnset of diabetesTransgenic T cellsCourse of diseaseType 1 diabetesFas-Fas ligand pathwayRelease of perforinSpontaneous diabetesAutoreactive CD4Lymph nodesImmune destructionLower incidenceBeta cellsDiabetesLigand pathwayPancreatic isletsTarget cellsThe role of TLR3 in protection of diabetes by PolyI:C in NOD mice (136.31)
Xiang Y, Wen L, Zhou Z, Wong F. The role of TLR3 in protection of diabetes by PolyI:C in NOD mice (136.31). The Journal Of Immunology 2010, 184: 136.31-136.31. DOI: 10.4049/jimmunol.184.supp.136.31.Peer-Reviewed Original ResearchRole of TLR3Adoptive transferProtective effectDiabetes developmentNon-hematopoietic cellsNOD micePoly IYoung WTBone marrow chimera experimentsOnset of diabetesAdoptive transfer modelExpression of TLR3Diabetic wild typeC administrationTLR3Chimera experimentsPolyIMiceRecipientsTreatmentDiabetesDisease developmentExogenous treatmentNODCells
2008
The Role of Toll‐Like Receptors 3 and 9 in the Development of Autoimmune Diabetes in NOD Mice
Wong FS, Hu C, Zhang L, Du W, Alexopoulou L, Flavell RA, Wen L. The Role of Toll‐Like Receptors 3 and 9 in the Development of Autoimmune Diabetes in NOD Mice. Annals Of The New York Academy Of Sciences 2008, 1150: 146-148. PMID: 19120284, DOI: 10.1196/annals.1447.039.Peer-Reviewed Original ResearchConceptsToll-like receptorsNOD miceHeterozygous miceToll-like receptor 3Different Toll-like receptorsTLR3-deficient miceTLR9-deficient miceRole of TLR3Type 1 diabetesDifferent microbial stimuliNumber of receptorsAutoimmune diabetesSpontaneous diabetesAutoimmune diseasesMicrobial stimuliAdaptive immunityInnate responseInnate immunityReceptor 3DiabetesMiceTLR3DiseaseImmunityReceptorsToll‐Like Receptors and Diabetes
Wong F, Wen L. Toll‐Like Receptors and Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 123-132. PMID: 19120280, DOI: 10.1196/annals.1447.063.Peer-Reviewed Original ResearchConceptsToll-like receptorsAntigen-presenting cellsType 1 interferonAdaptive immune systemRegulatory cellsAutoimmune responseInflammatory cytokinesMore specific responsesIFN-alphaImmune responseEndogenous ligandImmune systemMolecular patternsInfectionMicrobial infectionsReceptorsInterferonEndogenous stimuliDirect effectCellular stressSpecific responsesCellsResponseAutoimmunityDiabetesIFN‐α Can Both Protect against and Promote the Development of Type 1 Diabetes
Wong F, Wen L. IFN‐α Can Both Protect against and Promote the Development of Type 1 Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 187-189. PMID: 19120292, DOI: 10.1196/annals.1447.031.Peer-Reviewed Original Research