2024
Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes
Kakabadse D, Chen D, Fishman S, Weinstein-Marom H, Davies J, Wen L, Gross G, Wong F. Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes. Frontiers In Immunology 2024, 15: 1463971. PMID: 39351219, PMCID: PMC11439686, DOI: 10.3389/fimmu.2024.1463971.Peer-Reviewed Original ResearchCD8+ T cellsCD4+ T cellsAntigen-specific CD8+ T cellsDevelopment of autoimmune diabetesRegulatory T cellsCo-transfer experimentsT cellsNOD miceAutoimmune diabetesAntigen-specific CD4+ T cellsRegulatory CD4+ T cellsAntigen-specific cytotoxic CD8Pathogenic CD8+ T cellsPre-diabetic NOD micePolyclonal CD4+ T cellsDevelopment of type 1 diabetesSuppresses autoimmune diabetesAntigen-specific CD4Expression of Foxp3Young NOD miceT cell-T cellMarkers in vitroType 1 diabetesAdoptive transferTreg cellsTLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model
Pearson J, Hu Y, Peng J, Wong F, Wen L. TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model. Frontiers In Immunology 2024, 15: 1333967. PMID: 38482010, PMCID: PMC10935730, DOI: 10.3389/fimmu.2024.1333967.Peer-Reviewed Original ResearchConceptsToll-like receptor 5Antigen-presenting cellsDendritic cellsType 1 diabetesTLR5-deficientDC developmentCytokine secretionCD4<sup>+</sup> T cell proliferationPathogenesis of type 1 diabetesT cell responsesEnhanced cytokine secretionT cell proliferationWild-type miceSusceptibility to obesitySusceptibility to T1DProinflammatory cytokine secretionGut microbiotaSpontaneous T1DNOD miceAutoimmune diabetesNon-obeseHuman T1DReceptor 5Autoimmune diseasesHyper-secretion
2023
Novel engineered B lymphocytes targeting islet-specific T cells inhibit the development of type 1 diabetes in non-obese diabetic Scid mice
Chen D, Kakabadse D, Fishman S, Weinstein-Marom H, Davies J, Boldison J, Thayer T, Wen L, Gross G, Wong F. Novel engineered B lymphocytes targeting islet-specific T cells inhibit the development of type 1 diabetes in non-obese diabetic Scid mice. Frontiers In Immunology 2023, 14: 1227133. PMID: 37731505, PMCID: PMC10507356, DOI: 10.3389/fimmu.2023.1227133.Peer-Reviewed Original ResearchConceptsAntigen-specific CD8Islet-specific T cellsT cellsAutoimmune diabetesB cellsSCID miceMouse modelB lymphocytesNon-obese diabetic (NOD) mouse modelRegulatory B cell functionsProtective cell typesAntigen-specific CD4Pathogenic T cellsT cell cytotoxicityAntigen-presenting cellsCo-transfer experimentsDiabetic mouse modelDiabetic SCID miceType 1 diabetesAntigen-specific cellsB cell functionNovel therapeutic approachesMHC II moleculesSplenic B cellsPD-1NLRP6 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
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 rolePathogenesisLADADisease
2020
Mouse 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
Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs
Hu Y, Peng J, Tai N, Hu C, Zhang X, Wong FS, Wen L. Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs. The Journal Of Immunology 2015, 195: 4176-4184. PMID: 26401004, PMCID: PMC4765177, DOI: 10.4049/jimmunol.1500884.Peer-Reviewed Original ResearchConceptsNOD miceTolerogenic APCsDiabetes developmentT cell-mediated autoimmune diseaseDiabetogenic CD8 T cellsCell-mediated autoimmune diseasePolymyxin BCD8 T cellsNonobese diabetic (NOD) miceType 1 diabetesHost immune systemIslet β-cellsAutoimmune diabetesDifferent time pointsImmune toleranceDiabetic miceAutoimmune diseasesProfound protectionT cellsImmune responseProtective effectCommensal microbiotaGut microbiotaSusceptible individualsCommensal bacteria
2014
IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice
Tan Q, Majewska-Szczepanik M, Zhang X, Szczepanik M, Zhou Z, Wong FS, Wen L. IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice. Diabetes 2014, 63: 2761-2775. PMID: 24696448, PMCID: PMC4113073, DOI: 10.2337/db13-1504.Peer-Reviewed Original ResearchConceptsDiabetogenic T cellsNOD miceRapid progressionT cellsInterleukin-1 receptor-associated kinase MOrgan-specific autoimmune diseasesType 1 diabetes mellitusAnti-insulin autoantibodiesImmunodeficient NOD miceImpaired glucose toleranceAntigen-presenting functionNonobese diabetic (NOD) miceToll-like receptor pathwayAntigen-presenting cellsEnhanced activationType 1 diabetesInnate immune pathwaysIRAK-M deficiencyInnate immune processesInsulin-secreting pancreatic β-cellsPancreatic β-cellsSevere insulitisAutoimmune diabetesDendritic cellsDiabetes mellitusLong 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
The Dual Effects of B Cell Depletion on Antigen-Specific T Cells in BDC2.5NOD Mice
Xiang Y, Peng J, Tai N, Hu C, Zhou Z, Wong FS, Wen L. The Dual Effects of B Cell Depletion on Antigen-Specific T Cells in BDC2.5NOD Mice. The Journal Of Immunology 2012, 188: 4747-4758. PMID: 22490442, PMCID: PMC4361183, DOI: 10.4049/jimmunol.1103055.Peer-Reviewed Original ResearchConceptsB-cell depletionCell depletionT cellsB cellsAntigen-specific T cellsAg-specific T cellsBDC2.5 T cellsDiabetogenic T cellsRegulatory T cellsT cell responsesB-cell reconstitutionB-cell regenerationT-cell phenotypeImmune regulatory functionsFuture clinical protocolsΒ-cell lossMultiple injection protocolsAutoimmune diabetesRituximab therapyCytokine profileDiabetic patientsCell reconstitutionTherapeutic effectPreclinical studiesHuman CD20
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 Research
2009
Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice
Xiao X, Ma B, Dong B, Zhao P, Tai N, Chen L, Wong FS, Wen L. Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. Journal Of Autoimmunity 2009, 32: 85-93. PMID: 19200691, DOI: 10.1016/j.jaut.2008.12.003.Peer-Reviewed Original ResearchConceptsDiabetic NOD miceNOD miceDiabetic nephropathyDiabetic miceNon-diabetic NOD miceNon-obese diabetic (NOD) miceDuration of diabetesUrinary albumin excretionAdditional therapeutic targetsHumoral immune responseAlbumin excretionAutoimmune diabetesDendritic cellsDiabetes onsetImmune changesKidney weightIgG depositsHumoral immunityT cellsImmune responseNephropathyComplement C3Therapeutic targetB cellsImmune system
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 3DiabetesMiceTLR3DiseaseImmunityReceptorsIFN‐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 ResearchInnate 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 predispositionIncidence
2007
Role of Fas in Autoimmune Diabetes (128.30)
Mora C, Wen L, Gomis R, Green E, Chervonsky A, Wong F, García A, Flavell R. Role of Fas in Autoimmune Diabetes (128.30). The Journal Of Immunology 2007, 178: s216-s216. DOI: 10.4049/jimmunol.178.supp.128.30.Peer-Reviewed Original ResearchCD4 T cellsNOD miceΒ-cellsΒ-cell deathRole of FasAutoimmune diabetesIL-1βT cellsDiabetogenic CD4 T cellsDevelopment of diabetesCytokine-mediated inductionMouse β-cellsCell deathExpression of FasIslet antigensDiabetes incidenceImmune toleranceKey cytokineDiabetic phenotypeEarly overexpressionDiabetesIslet cellsFas expressionFasL overexpressionMice
2005
B cells in autoimmune diabetes.
Wong FS, Wen L. B cells in autoimmune diabetes. The Review Of Diabetic Studies 2005, 2: 121-35. PMID: 17491687, PMCID: PMC1783559, DOI: 10.1900/rds.2005.2.121.Peer-Reviewed Original ResearchAutoimmune diabetesB cellsNon-obese diabetic (NOD) mouse modelAutoantigen-specific B cellsType 1 diabetes mellitusAntigen-presenting functionDiabetic mouse modelAutoreactive B cellsB cell toleranceSpecific B cellsHuman T1DMDiabetes mellitusMouse modelCell toleranceAutoantibodiesGood markerDiabetesPathogenesisDiseaseCellsAspects of deficienciesCritical roleMellitusT1DMThe Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice
Wong FS, Du W, Thomas IJ, Wen L. The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice. Diabetes 2005, 54: 2032-2040. PMID: 15983204, DOI: 10.2337/diabetes.54.7.2032.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IHistocompatibility Antigens Class IIIslets of LangerhansLymphocyte DepletionMajor Histocompatibility ComplexMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDConceptsT cell repertoireMajor histocompatibility complexI-Ag7Autoimmune T cell repertoireImportant genetic susceptibility factorAutoreactive T cell repertoireBALB/c miceHistocompatibility complexNonobese-resistant miceRIP-B7.1 miceCD8 T cellsNonobese diabetic (NOD) miceMHC class II moleculesDiabetes-resistant miceType 1 diabetesIslet beta cellsClass II moleculesCostimulatory molecule B7.1MHC class IC57BL/6 genetic backgroundGenetic susceptibility factorsLocal costimulationAutoimmune diabetesNOD miceSpontaneous diabetes
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