2024
Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice
Yang X, Xu Y, Li J, Ran X, Gu Z, Song L, Zhang L, Wen L, Ji G, Wang R. Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice. MSystems 2024, 9: e00127-24. PMID: 38934542, PMCID: PMC11265269, DOI: 10.1128/msystems.00127-24.Peer-Reviewed Original ResearchGut microbiotaGut microbiota dysbiosisDysregulated gut microbiotaGut microbiota transplantationGerm-free miceVirulence factorsSmall intestinal bacteriaBile acid homeostasisMicrobiota dysbiosisDecreased diversityMicrobiota imbalanceMicrobiotaMouse model of cholestasisBile acidsMouse modelIntestinal bacteriaAcid homeostasisMicrobiota transplantationClinical management of patientsGutHepatic bile acidsLong-term effectsPre-clinical findingsModel of cholestasisManagement of patients
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
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 ResearchConceptsType 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 mechanismsCD28TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model.
Sha S, Pearson JA, Peng J, Hu Y, Huang J, Xing Y, Zhang L, Zhu Y, Zhao H, Wong FS, Chen L, Wen L. TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model. Diabetes 2020, 70: 504-515. PMID: 33154070, PMCID: PMC7881860, DOI: 10.2337/db20-0373.Peer-Reviewed Original ResearchConceptsToll-like receptor 9B cellsNOD miceInterleukin-10IL-10-producing B cellsType 1 diabetes developmentAdaptive immune stimuliΒ-cell autoimmunityB-cell-specific deficiencyNovel therapeutic strategiesInnate immune moleculesB cell-specific deletionT1D developmentDiabetes protectionIL-10TLR9 deficiencyImmune toleranceDiabetes developmentReceptor 9T1D treatmentTLR9 pathwayImmune stimuliMouse modelTherapeutic strategiesMetalloproteinase-1Mouse 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
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
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 modelBregs
2009
Inflammatory Regulation by TLR3 in Acute Hepatitis
Xiao X, Zhao P, Rodriguez-Pinto D, Qi D, Henegariu O, Alexopoulou L, Flavell RA, Wong FS, Wen L. Inflammatory Regulation by TLR3 in Acute Hepatitis. The Journal Of Immunology 2009, 183: 3712-3719. PMID: 19710451, PMCID: PMC3787866, DOI: 10.4049/jimmunol.0901221.Peer-Reviewed Original ResearchConceptsAcute hepatitisCon ATLR3 expressionLiver damageAdaptive T cell immune responseBone marrow chimeric miceT cell immune responsesCon A injectionFunction of TLR3Hematopoietic cellsLiver mononuclear cellsCell immune responsesDamaged liver tissueWild-type miceWT hematopoietic cellsA injectionWT miceMononuclear cellsInnate activationHepatocyte damageImmune responseInflammatory regulationHepatitisMouse modelTLR3
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 roleMellitusT1DM
2002
Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide
Moriyama H, Wen L, Abiru N, Liu E, Yu L, Miao D, Gianani R, Wong F, Eisenbarth G. Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 5539-5544. PMID: 11943868, PMCID: PMC122805, DOI: 10.1073/pnas.082120099.Peer-Reviewed Original ResearchConceptsT lymphocytesB7-1 transgenic miceBALB/c miceAnti-islet autoimmunityExperimental autoimmune diabetesAutoreactive T lymphocytesB7-1 moleculeCD4 T lymphocytesType 1 diabetesPolyinosinic-polycytidylic acidAutoimmune diabetesInsulin autoantibodiesC micePeptide immunizationSimultaneous administrationDisease inductionMurine modelMouse modelDiabetesTransgenic miceInsulin peptidesMiceImmunizationPolyICViral mimic