2023
NLRP6 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
2020
Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice
Pearson JA, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y, Wong FS, Wen L. Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice. Frontiers In Immunology 2020, 11: 585886. PMID: 33262765, PMCID: PMC7688534, DOI: 10.3389/fimmu.2020.585886.Peer-Reviewed Original ResearchConceptsB cell interactionsTransgenic NOD miceNOD miceT cellsB cellsT1D developmentAntigen-specific regulatory T cellsInsulin-reactive B cellsInsulin-reactive T cellsNon-obese diabetic (NOD) miceGerminal center TInsulin-reactive CD4Non-germinal centerCell interactionsCostimulatory molecule expressionRegulatory T cellsType 1 diabetesGC B cellsTolerogenic cellsAdoptive transferDiabetic miceTGFβ secretionMolecule expressionIgG isotypeKey autoantigenMouse 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
2016
The Gut Microbiome in the NOD Mouse
Peng J, Hu Y, Wong FS, Wen L. The Gut Microbiome in the NOD Mouse. Methods In Molecular Biology 2016, 1433: 169-177. PMID: 27032947, DOI: 10.1007/7651_2016_331.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentNOD miceDiabetes developmentGut bacteriaSusceptible NOD miceNonobese diabetic (NOD) miceBacterial DNA sequencingGut microbiome compositionGut microbiome analysisMouse fecal samplesExcellent mouse modelDiabetic miceMouse modelGut microbiotaGut microbiomeIntestinal contentsMiceCritical modulatorDisease phenotypeFecal samplesMicrobiome compositionStandard protocolMicrobiome analysisHealthPathogenic microorganisms
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
Toll-Like Receptor 3 Is Critical for Coxsackievirus B4-Induced Type 1 Diabetes in Female NOD Mice
McCall K, Thuma J, Courreges M, Benencia F, James C, Malgor R, Kantake N, Mudd W, Denlinger N, Nolan B, Wen L, Schwartz F. Toll-Like Receptor 3 Is Critical for Coxsackievirus B4-Induced Type 1 Diabetes in Female NOD Mice. Endocrinology 2014, 156: 453-461. PMID: 25422874, PMCID: PMC4298321, DOI: 10.1210/en.2013-2006.Peer-Reviewed Original ResearchConceptsToll-like receptor 3TLR3 knockout miceWild-type miceNOD miceKnockout miceRole of TLR3Receptor 3Type 1 diabetes mellitusFemale NOD miceProne NOD miceNonobese diabetic (NOD) miceIncidence of diabetesType 1 diabetesViral double-stranded RNAGroup B coxsackievirusesHuman T1DMDiabetes mellitusDiabetic miceMouse modelT1DMTLR3 knockoutUninfected counterpartsUninfected animalsB coxsackievirusesInsulitisInterleukin-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 modelBregsLong 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
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
2012
Correction: 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
2009
Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice
Hamilton-Williams EE, Martinez X, Clark J, Howlett S, Hunter KM, Rainbow DB, Wen L, Shlomchik MJ, Katz JD, Beilhack GF, Wicker LS, Sherman LA. Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice. The Journal Of Immunology 2009, 183: 1533-1541. PMID: 19592648, PMCID: PMC2733871, DOI: 10.4049/jimmunol.0900428.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT cellsDendritic cellsNOD miceProtective allelesCD4 T-cell expressionTolerance defectsImmune tolerance resultsPancreatic lymph nodesCD8 T cellsNonobese diabetic (NOD) miceCD4 T cellsT cell expressionLoss of toleranceIL-2 productionDiabetes 3Lymph nodesDiabetic miceIslet AgsNOD alleleCell expressionMiceSpontaneous developmentIdd3Tolerance resultsActivation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes
Wong FS, Siew LK, Scott G, Thomas IJ, Chapman S, Viret C, Wen L. Activation of Insulin-Reactive CD8 T-Cells for Development of Autoimmune Diabetes. Diabetes 2009, 58: 1156-1164. PMID: 19208910, PMCID: PMC2671054, DOI: 10.2337/db08-0800.Peer-Reviewed Original ResearchConceptsCD8 T cellsCD8 T cell clonesT cell clonesT cellsTransgenic miceT cell receptor transgenic miceAutoimmune CD8 T cellsInsulin-reactive T cellsCD8 single-positive thymocytesNonobese diabetic (NOD) miceReceptor transgenic miceDevelopment of autoimmuneTCR transgenic miceTransgenic T cellsThymic negative selectionSingle-positive thymocytesThymic insulin expressionDiabetogenic capacityIslet infiltratesSpontaneous diabetesPeripheral lymphClonotypic TCRDiabetic miceImmunodeficient NODNaïve phenotypeCellular 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
2007
Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice
Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, Shlomchik MJ, Wen L. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. Journal Of Clinical Investigation 2007, 117: 3857-3867. PMID: 18060033, PMCID: PMC2096456, DOI: 10.1172/jci32405.Peer-Reviewed Original ResearchConceptsB-cell depletionCell depletionB cellsNOD miceTherapeutic B cell depletionTransgenic NOD miceRegulatory B cellsLong-term remissionExpansion of TregsOnset of diabetesType 1 diabetesReverse diabetesClinical efficacyDiabetic miceAutoimmune diseasesFrank hyperglycemiaAntigen presentationT cellsHuman CD20DiabetesTherapeutic actionMiceClinical hyperglycemiaDiseasePotential mechanismsCD86 Has Sustained Costimulatory Effects on CD8 T Cells
Thomas IJ, de Marquesini L, Ravanan R, Smith RM, Guerder S, Flavell RA, Wraith DC, Wen L, Wong FS. CD86 Has Sustained Costimulatory Effects on CD8 T Cells. The Journal Of Immunology 2007, 179: 5936-5946. PMID: 17947667, PMCID: PMC2629533, DOI: 10.4049/jimmunol.179.9.5936.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-1 AntigenB7-2 AntigenCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationCells, CulturedCytokinesDiabetes MellitusGene Expression RegulationHealthHumansIslets of Langerhans TransplantationMiceMice, TransgenicPromoter Regions, GeneticRatsReceptor, InsulinSurvival RateTime FactorsTransgenesConceptsCD8 T cellsT cellsT cell activationCD86 costimulationCell activationCytotoxic T-cell activationTransfer of diabetesOld NOD miceInhibitory molecule expressionRat insulin promoterGreater sustained activityNOD isletsRecurrent diabetesNOD miceDiabetes onsetDiabetic miceCostimulatory moleculesCTLA-4Cytokine secretionMolecule expressionCostimulatory effectImmune responseCD80CD86CD80 costimulation
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
1999
Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library
Wong F, Karttunen J, Dumont C, Wen L, Visintin I, Pilip I, Shastri N, Pamer E, Janeway C. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nature Medicine 1999, 5: 1026-1031. PMID: 10470079, DOI: 10.1038/12465.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAutoantigensCD8-Positive T-LymphocytesClone CellsCloning, MolecularCOS CellsDiabetes Mellitus, Type 1Epitopes, T-LymphocyteGene LibraryHistocompatibility Antigens Class IInsulinInterferon-gammaIslets of LangerhansLymphocyte ActivationLymphocyte CountMiceMice, Inbred NODMice, Inbred StrainsOrgan SpecificityPeptidesConceptsType 1 diabetesAutoimmune diseasesT cellsPathogenic CD4 T cellsPathogenic CD8 T cellsNon-obese diabetic (NOD) miceCD8 T cell epitopesInsulin-producing pancreatic β-cellsAntigen-specific immunotherapyCD8 T lymphocytesCD8 T cellsCD4 T cellsT cell epitopesGood animal modelMHC class IIdentification of autoantigensPancreatic β-cellsDiabetic micePreventative therapyHuman diabetesT lymphocytesAnimal modelsImmune processesDiabetesΒ-cells
1998
The Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice
Wong F, Visintin I, Wen L, Granata J, Flavell R, Janeway C. The Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice. Journal Of Experimental Medicine 1998, 187: 1985-1993. PMID: 9625758, PMCID: PMC2212360, DOI: 10.1084/jem.187.12.1985.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAge of OnsetAnimalsAntigen PresentationB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IIncidenceInsulinIslets of LangerhansLymphocyte SubsetsMiceMice, Inbred NODMice, TransgenicPromoter Regions, GeneticSpleenConceptsCD8 T cellsT cellsNOD miceB cellsAccelerated diabetesDiabetic miceB7-1 transgenic micePeripheral CD8 T cellsEffective antigen-presenting cellsMajor histocompatibility complex class IInsulin promoterCD4-/- miceMuMT-/- miceNontransgenic NOD miceNormal NOD miceNonobese diabetic (NOD) miceCD4 T cellsHistocompatibility complex class IAntigen-presenting cellsProvision of costimulationComplex class IPancreatic beta cellsWk of ageB220-positive B cellsIslet infiltrates
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