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 ResearchMeSH KeywordsAnimalsAutoantibodiesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2HumansImmunity, InnateLatent Autoimmune Diabetes in AdultsRatsConceptsType 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
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 ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDendritic CellsDiabetes Mellitus, Type 1Histocompatibility Antigens Class IILymph NodesMiceMice, Inbred NODProinsulinStromal CellsConceptsType 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 mechanismsCD28A predictive CD8+ T cell phenotype for T1DM progression
Wong FS, Wen L. A predictive CD8+ T cell phenotype for T1DM progression. Nature Reviews Endocrinology 2020, 16: 198-199. PMID: 32051538, PMCID: PMC8258660, DOI: 10.1038/s41574-020-0330-3.Peer-Reviewed Original Research
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
The 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
2010
Immunotargeting 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 cells
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
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 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 predispositionIncidenceCD8+ T-cells and their interaction with other cells in damage to islet β-cells
Wong F, Siew L, Wen L. CD8+ T-cells and their interaction with other cells in damage to islet β-cells. Biochemical Society Transactions 2008, 36: 316-320. PMID: 18481949, DOI: 10.1042/bst0360316.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell CommunicationHumansImmune SystemInsulin-Secreting CellsLymphocyte ActivationConceptsT cellsHuman type 1 diabetesAntigen-presenting cellsType 1 diabetesAutoimmune attackDiabetes developmentAntigenic targetsEffector stageToxic mediatorsVariety of cellsAnimal modelsTarget antigenImmune systemΒ-cellsMechanisms of damageCellsEarly stagesDamageCD8DiabetesCytokinesLymphocytesAntigen
2007
Functional inhibition related to structure of a highly potent insulin‐specific CD8 T cell clone using altered peptide ligands
de Marquesini L, Moustakas A, Thomas I, Wen L, Papadopoulos G, Wong F. Functional inhibition related to structure of a highly potent insulin‐specific CD8 T cell clone using altered peptide ligands. European Journal Of Immunology 2007, 38: 240-249. PMID: 18157812, PMCID: PMC2901522, DOI: 10.1002/eji.200737762.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsCD8 T cell clonesAntagonist activityT cell functionT cell clonesProduction assaysMHC-peptide complexesTCR contact sitesNOD miceCD8 epitopesAgonist responsesTherapeutic useFunctional inhibitionCell clonesTCR stimulationCell functionPeptide ligandsNative peptideCellsPeptidesCytotoxicityAPLAssaysCD4CD86 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
2005
The 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
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
2002
Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus
Wong F, Moustakas A, Wen L, Papadopoulos G, Janeway C. Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 5551-5556. PMID: 11943852, PMCID: PMC122807, DOI: 10.1073/pnas.072037299.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensCD8-Positive T-LymphocytesCell DivisionCell LineChromium RadioisotopesDiabetes Mellitus, Type 1Dose-Response Relationship, DrugH-2 AntigensInsulinInterferon-gammaMiceMice, Inbred NODModels, MolecularPeptidesProtein BindingReceptor, InsulinStructure-Activity RelationshipTime FactorsConceptsT cellsCD8 T cell clonesInsulin-dependent diabetes mellitusInduction of CD8CD8 T cellsPathogenic T cellsT cell clonesT cell stimulationSmall glycine residueMHC-peptide complexesDiabetes mellitusAutoantigenic peptidesH-2KdCell clonesGlutamate residuesHydrophobic residuesGlycine residueReceptor interaction sitesCell stimulationFunctional assaysInteraction sitesFunction relationshipsPeptide substitutionProductive interactionHeavy chain
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
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