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 ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Immune ToleranceInflammasomesInterleukin-10LipopolysaccharidesMiceMice, Inbred NODConceptsNlrp6-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
IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice
Huang J, Tan Q, Tai N, Pearson JA, Li Y, Chao C, Zhang L, Peng J, Xing Y, Zhang L, Hu Y, Zhou Z, Wong FS, Wen L. IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice. Frontiers In Immunology 2021, 12: 702955. PMID: 34394099, PMCID: PMC8362616, DOI: 10.3389/fimmu.2021.702955.Peer-Reviewed Original ResearchConceptsNOD miceProportion of neutrophilsT cellsGut microbiotaDiabetes developmentT cell-mediated destructionT cell receptor transgenicType 1 diabetes developmentAccelerated diabetes developmentInhibition of diabetesModulation of InnatePathogenicity of CD4Cell-mediated destructionAdaptive immune cellsObese diabetic miceT regulatory (Treg) cellsDevelopment of diabetesPrevention of diabetesActivation of CD4Modulation of neutrophilsType 1 diabetesGut microbiota compositionInsulin-producing β-cellsSevere insulitisSpontaneous diabetesToll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Huang J, Peng J, Pearson JA, Efthimiou G, Hu Y, Tai N, Xing Y, Zhang L, Gu J, Jiang J, Zhao H, Zhou Z, Wong FS, Wen L. Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function. Cellular & Molecular Immunology 2021, 18: 328-338. PMID: 33432061, PMCID: PMC8027372, DOI: 10.1038/s41423-020-00590-8.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentToll-like receptorsType 1 diabetesDiabetes developmentB cellsTLR7 deficiencyNOD miceB cell differentiationT cellsClassical MHC class I moleculesHuman type 1 diabetesImmunodeficient NOD miceNOD B cellsDiabetogenic T cellsAntigen-presenting functionNonobese diabetic (NOD) miceT cell responsesB cell functionMHC class I moleculesPattern recognition receptorsT cell activationPathogen molecular patternsClass I moleculesDiabetogenic CD4Cytotoxic CD8
2019
Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions
Pearson JA, Tai N, Ekanayake-Alper DK, Peng J, Hu Y, Hager K, Compton S, Wong FS, Smith PC, Wen L. Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions. Frontiers In Immunology 2019, 10: 2654. PMID: 31798584, PMCID: PMC6863139, DOI: 10.3389/fimmu.2019.02654.Peer-Reviewed Original ResearchConceptsExpansion of TregsNOD miceT cellsMNV4 infectionMucosal immunityNon-obese diabetic (NOD) mouse modelGerm-free NOD miceFirmicutes/Bacteroidetes ratioProinflammatory T cellsRole of norovirusesTuft cell markersDevelopment of T1DInflammatory T cellsCommon enteric virusesB cell subsetsDiabetic mouse modelImmune cell functionType 1 diabetes susceptibilityEnteric virusesNaïve splenocytesT1D protectionTreg numbersImmunological changesMucosal antibodiesT1D development
2018
Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and function in a mouse model of type 1 diabetes
Liu M, Peng J, Tai N, Pearson JA, Hu C, Guo J, Hou L, Zhao H, Wong FS, Wen L. Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and function in a mouse model of type 1 diabetes. Diabetologia 2018, 61: 2333-2343. PMID: 30094467, PMCID: PMC6182661, DOI: 10.1007/s00125-018-4705-0.Peer-Reviewed Original ResearchConceptsToll-like receptorsType 1 diabetesRole of TLR9Beta-cell functionNOD miceBeta-cell developmentBeta cellsGlucose toleranceTLR9 antagonistFirst-phase insulin secretory responseInnate immune Toll-like receptorsRole of TLRsImmune Toll-like receptorsWild-type NOD miceType 1 diabetes developmentToll-like receptor 9Absence of TLR9Cell functionIslet beta-cell growthBeta cell numberInsulin secretory responseEnhanced glucose toleranceIslet beta cellsPotential therapeutic targetBeta-cell growthTRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells
Gülden E, Chao C, Tai N, Pearson JA, Peng J, Majewska-Szczepanik M, Zhou Z, Wong FS, Wen L. TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells. Journal Of Autoimmunity 2018, 93: 57-65. PMID: 29960834, PMCID: PMC6108920, DOI: 10.1016/j.jaut.2018.06.003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAdoptive TransferAnimalsBacteroidetesBurkholderialesCell ProliferationDendritic CellsDiabetes Mellitus, ExperimentalDisease SusceptibilityFemaleFirmicutesGastrointestinal MicrobiomeGene Expression RegulationLymphocyte ActivationMiceMice, Inbred NODMice, KnockoutMyeloid Differentiation Factor 88Signal TransductionT-LymphocytesToll-Like Receptor 3Toll-Like Receptor 4ConceptsWT NOD miceNOD miceType 1 diabetesGut microbiotaDiabetes developmentDendritic cellsCell activationNon-obese diabetic (NOD) mouse modelMyeloid differentiation primary response gene 88Wild-type NOD miceNon-obese diabetic (NOD) miceToll-like receptor signalingDiabetes susceptibilityStrong inflammatory immune responseDevelopment of diabetesInflammatory immune responseDiabetic mouse modelAdapter-inducing interferonImmune cell activationT cell activationTRIF deficiencyAdaptor protein downstreamFurther immunological analysisHuman T1D.T1D developmentActivation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice
Tan Q, Tai N, Li Y, Pearson J, Pennetti S, Zhou Z, Wong FS, Wen L. Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice. JCI Insight 2018, 3: e95882. PMID: 29321370, PMCID: PMC5821212, DOI: 10.1172/jci.insight.95882.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAutoantibodiesAutoimmunityB-LymphocytesCytidine DeaminaseCytokinesDiabetes Mellitus, Type 1Enzyme ActivationFemaleGene Knockdown TechniquesImmune ToleranceImmunoglobulin AImmunoglobulin GInsulinInterferon-gammaLymph NodesMaleMiceMice, Inbred NODMilkPlacentaPregnancySpleenT-LymphocytesVirulenceConceptsDiabetes developmentB cellsT cellsNOD miceActivation-induced cytidine deaminaseType 1 diabetes developmentAccelerated diabetes developmentAnti-insulin autoantibodiesIFN-γ expressionMore rapid onsetB cell interactionsRole of AIDAccelerated T1DActivation-induced cytidine deaminase (AID) deficiencyAutoimmune diabetesIslet autoimmunityT1D developmentImmune toleranceMaternal IgGT-betRapid onsetPresence of AIDMiceDeaminase deficiencyCD4
2016
Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice
Tai N, Peng J, Liu F, Gulden E, Hu Y, Zhang X, Chen L, Wong FS, Wen L. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice. Journal Of Experimental Medicine 2016, 213: 2129-2146. PMID: 27621416, PMCID: PMC5030808, DOI: 10.1084/jem.20160526.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, BacterialCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, ExperimentalFemaleGastrointestinal MicrobiomeGlucose-6-PhosphataseLymphocyte ActivationMice, Inbred C57BLMice, Inbred NODMyeloid Differentiation Factor 88PeptidesReceptors, Antigen, T-CellThymus GlandT-Lymphocytes, RegulatoryConceptsCD8 T cellsT cellsCommensal bacteriaSignificant homologyDiabetes developmentGut microbiotaDiabetogenic CD8 T cellsPathogenic CD8 T cellsTransgenic nonobese diabetic miceGut microbesType 1 diabetes developmentIslet-specific glucose-6-phosphatase catalytic subunit-related proteinNovel mechanismNonobese diabetic (NOD) miceInnate immunityBacteriaMolecular mimicryNOD miceIslet autoantigensT1D developmentDiabetic miceMicrobial antigensCellsAnimal modelsHuman studiesThe induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model
Yuksel M, Xiao X, Tai N, Vijay M, Gülden E, Beland K, Lapierre P, Alvarez F, Hu Z, Colle I, Ma Y, Wen L. The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model. Clinical & Experimental Immunology 2016, 186: 164-176. PMID: 27414259, PMCID: PMC5054566, DOI: 10.1111/cei.12843.Peer-Reviewed Original ResearchMeSH KeywordsAmmonia-LyasesAnimalsAntigen-Presenting CellsAutoantibodiesAutoantigensCD8-Positive T-LymphocytesCytochrome P-450 CYP2D6CytokinesDisease Models, AnimalGlutamate FormimidoyltransferaseHepatitis, AutoimmuneHLA-DR4 AntigenHumansHypergammaglobulinemiaImmunizationImmunoglobulin GInflammation MediatorsMiceMice, Inbred NODMice, TransgenicMultienzyme ComplexesMultifunctional EnzymesPlasma CellsT-Lymphocyte SubsetsConceptsDevelopment of AIHAutoimmune hepatitisHLA-DR4DR4 miceT cellsAnti-liver kidney microsomal type 1Anti-liver cytosol type 1Induction of AIHWild-type NOD miceNon-obese diabetic (NOD) miceType 1Key immune cell subsetsAnti-smooth muscle actinAdult autoimmune hepatitisHepatitis mouse modelElevated alanine aminotransferasePD-1 expressionPlasma cell infiltrationChronic liver diseaseRegulatory T cellsMild liver injuryImmune cell subsetsPersistent liver damageAntigen-presenting cellsHuman leucocyte antigenThe role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes
Tai N, Wong FS, Wen L. The role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes. Journal Of Autoimmunity 2016, 71: 26-34. PMID: 27021275, PMCID: PMC4903935, DOI: 10.1016/j.jaut.2016.03.006.Peer-Reviewed Original ResearchConceptsPattern recognition receptorsToll-like receptorsInnate immunityCell autoimmunityAdaptive immunityHuman studiesOrgan-specific autoimmune diseasesT cell-mediated destructionΒ-cellsInsulin-producing pancreatic β-cellsDifferent pattern recognition receptorsCell-mediated destructionDevelopment of T1D.Pathogenesis of T1D.Type 1 diabetesFunctional β-cell massNovel therapeutic strategiesInnate immune responseInnate immune systemΒ-cell massPancreatic beta cellsShape adaptive immunityPancreatic β-cellsIslet β-cellsNOD mice
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 bacteriaA novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation
Yuksel M, Wang Y, Tai N, Peng J, Guo J, Beland K, Lapierre P, David C, Alvarez F, Colle I, Yan H, Mieli-Vergani G, Vergani D, Ma Y, Wen L. A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation. Hepatology 2015, 62: 1536-1550. PMID: 26185095, PMCID: PMC4763614, DOI: 10.1002/hep.27998.Peer-Reviewed Original ResearchConceptsAnti-liver cytosol type 1 autoantibodiesAnti-liver kidney microsomal type 1Autoimmune hepatitisHLA-DR3Type 1Antigenic targetsAntinuclear autoantibodiesAnti-liver cytosol type 1T helper 1 immune responseHelper 1 immune responsePathogenesis of AIHSevere inflammatory liver diseaseTypes of AIHHLA-DR3 transgenic miceAnti-smooth muscleInflammatory liver diseaseAssociation of HLANonobese diabetic (NOD) miceRegulatory T cellsImmune cell infiltrationNovel mouse modelNonobese diabetic (NOD) backgroundHumanized animal modelsFormiminotransferase cyclodeaminaseAIH-1
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
TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes
Dong B, Qi D, Yang L, Huang Y, Xiao X, Tai N, Wen L, Wong F. TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. AJP Heart And Circulatory Physiology 2012, 303: h732-h742. PMID: 22842069, PMCID: PMC3468457, DOI: 10.1152/ajpheart.00948.2011.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBlood GlucoseCell LineDiabetes Mellitus, Type 1Diabetic CardiomyopathiesDisease Models, AnimalFatty Acids, NonesterifiedJNK Mitogen-Activated Protein KinasesLipid MetabolismLipoprotein LipaseMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMyeloid Differentiation Factor 88MyocardiumMyocytes, CardiacOleic AcidP38 Mitogen-Activated Protein KinasesPhosphorylationRatsRNA InterferenceTime FactorsToll-Like Receptor 4TriglyceridesConceptsDiabetic heart diseaseType 1 diabetesHeart diseaseNOD animalsLipoprotein lipaseLipid accumulationNonobese diabetic (NOD) mouse modelLeft ventricular developed pressureCardiac fatty acid metabolismMyeloid differentiation primary response geneCardiac lipid accumulationControl nondiabetic miceGreater ejection fractionRole of TLR4Nonobese diabetic (NOD) miceOnset of diabetesVentricular developed pressureDevelopment of diabetesToll-like receptorsGreater fractional shorteningDiabetic mouse modelPlasma triglyceride levelsWild-type NODLower triglyceride accumulationCellular lipid accumulationThe 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
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