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-1
2015
NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets
Hu C, Ding H, Li Y, Pearson JA, Zhang X, Flavell RA, Wong FS, Wen L. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 11318-11323. PMID: 26305961, PMCID: PMC4568693, DOI: 10.1073/pnas.1513509112.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCarrier ProteinsCell MovementChemokine CCL5Chemokine CXCL10ChemotaxisDiabetes Mellitus, Type 1Gene ExpressionHumansInflammasomesInterferon Regulatory Factor-1Interleukin-1betaIslets of LangerhansMice, Inbred C57BLMice, Inbred NODMice, KnockoutMice, SCIDNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, CCR5Receptors, CXCR3Reverse Transcriptase Polymerase Chain ReactionSignal TransductionTime FactorsT-LymphocytesConceptsType 1 diabetesLeucine-rich repeatsNonobese diabetic (NOD) mouse modelPancreatic isletsRegulation of chemotaxisTreatment of T1D.Role of TLRsDevelopment of T1DChemokine receptor CCR5Diabetic mouse modelT cell migrationT cell activationPresence of NLRP3Pancreatic islet cellsNLRP3 ablationOligomerization domainNLRP3 inflammasomeReceptor CCR5T cellsTh1 differentiationInflammasome pathwayAdaptive immunityMouse modelAnimal modelsIslet cells
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 modelBregsIRAK-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 mellitus
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 predispositionIncidence
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 mechanisms
2006
TGF-β signaling is required for the function of insulin-reactive T regulatory cells
Du W, Wong FS, Li MO, Peng J, Qi H, Flavell RA, Sherwin R, Wen L. TGF-β signaling is required for the function of insulin-reactive T regulatory cells. Journal Of Clinical Investigation 2006, 116: 1360-1370. PMID: 16670772, PMCID: PMC1451206, DOI: 10.1172/jci27030.Peer-Reviewed Original ResearchConceptsT cellsNOD miceRegulatory cellsDominant negative TGF-beta receptor type IITransgenic miceTCR transgenic T cellsTGF-beta receptor type IIDiabetic NOD miceDiabetogenic spleen cellsDiabetogenic T cellsTCR transgenic miceTransgenic T cellsReceptor type IIBDC2.5 miceAdoptive transferTGF-beta signalingSpleen cellsParacrine mannerGranule antigensAutocrine mannerSuppressive propertiesDiabetesMiceTarget cellsSpontaneous development
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
1998
Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation.
Wen L, Barber D, Pao W, Wong F, Owen M, Hayday A. Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. The Journal Of Immunology 1998, 160: 1965-74. PMID: 9469460, DOI: 10.4049/jimmunol.160.4.1965.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisB-LymphocytesCD4 AntigensCell DifferentiationCells, CulturedClone CellsCytokinesFas Ligand ProteinFas ReceptorGene ExpressionImmunoglobulin Class SwitchingImmunoglobulin IsotypesImmunophenotypingMembrane GlycoproteinsMiceMice, KnockoutMice, SCIDMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaTh1 CellsTh2 CellsConceptsAlpha beta T cellsBeta T cellsGamma delta cellsT cellsCell clonesTh1/Th2 cellsGamma delta T cellsCD8 alpha betaDelta cellsDelta T cellsDivision of CD4Association of CD4Autoimmune diseasesCytokine expressionImmunoregulatory roleTh2 phenotypeTh2 subsetsTh2 cellsAntigen presentationCD4 expressionTh2 differentiationCD4Clonal levelAlpha betaStrong association
1996
Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.
Wen L, Pao W, Wong FS, Peng Q, Craft J, Zheng B, Kelsoe G, Dianda L, Owen MJ, Hayday AC. Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells. Journal Of Experimental Medicine 1996, 183: 2271-2282. PMID: 8642336, PMCID: PMC2192585, DOI: 10.1084/jem.183.5.2271.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesClone CellsFlow CytometryGerminal CenterHumansImmunoglobulin Class SwitchingImmunoglobulin EImmunoglobulin GLupus Erythematosus, SystemicLymphocyte DepletionMiceMice, Inbred NODMice, Inbred StrainsMice, KnockoutMice, SCIDReceptors, Antigen, T-Cell, alpha-betaSpleenT-LymphocytesConceptsSystemic lupus erythematosusBeta T cellsAlpha/beta T cellsGamma/delta T cellsDelta T cellsT cell helpT cellsT cell receptorCell helpT cell-mediated conditionsHuman systemic lupus erythematosusSevere combined immunodeficient (SCID) miceDevelopment of autoantibodiesCombined Immunodeficient MiceT-cell immunodeficiencyClass-switched antibodiesB cell collaborationGerminal center formationLupus erythematosusAutoantibody productionLymphoid folliclesImmunoglobulin class switchingIgE synthesisAlpha/betaCell immunodeficiencyCD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. Journal Of Experimental Medicine 1996, 183: 67-76. PMID: 8551245, PMCID: PMC2192404, DOI: 10.1084/jem.183.1.67.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenBase SequenceCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesClone CellsCytokinesDiabetes Mellitus, Type 2FemaleImmunohistochemistryImmunotherapy, AdoptiveInsulinIslets of LangerhansLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDMolecular Sequence DataPancreasPerforinPore Forming Cytotoxic ProteinsPromoter Regions, GeneticConceptsT cell linesNOD miceT cellsCD8 T cell linesCD8 T cell clonesNonobese diabetic (NOD) miceCB17 SCID miceCD4 T cellsPathogenesis of diabetesT cell clonesCell linesIslets of LangerhansT cell antigen receptorNOD isletsCD4 cellsLymphocytic infiltrateNOD-SCIDDiabetic miceDiabetic isletsFemale NODRapid onsetCell antigen receptorH-2KdAntigen receptorMice