2024
Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl mice
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-1NLRP6 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
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 ResearchConceptsType 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 rolePathogenesisLADADiseaseToll-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
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 autoantigenTLR9 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-1
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 modelBregs
2013
Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes
Hu C, Ding H, Zhang X, Wong FS, Wen L. Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes. Diabetes 2013, 62: 2849-2858. PMID: 23447122, PMCID: PMC3717853, DOI: 10.2337/db12-1175.Peer-Reviewed Original ResearchConceptsT cellsNOD miceB cellsT cell-mediated autoimmune diseaseB cell-directed therapiesB cell depletion therapyCell-mediated autoimmune diseaseDiabetic NOD miceTransgenic NOD miceRegulatory T cellsCD4 T cellsCell-directed therapiesAnti-CD3 treatmentType 1 diabetesCD20 monotherapyImportant preclinical evidenceDepletion therapyT1D developmentDendritic cellsIL-10Preclinical evidenceFurther mechanistic studiesAutoimmune diseasesAnti-CD20Suppressive function
2012
Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes.
Wong F, Wen L. Type 1 diabetes therapy beyond T cell targeting: monocytes, B cells, and innate lymphocytes. The Review Of Diabetic Studies 2012, 9: 289-304. PMID: 23804267, PMCID: PMC3740697, DOI: 10.1900/rds.2012.9.289.Peer-Reviewed Original ResearchConceptsInnate lymphocytesB cellsT cell targetingNatural killer cellsRecent clinical trialsPathogenesis of T1DType 1 diabetesType 1 diabetes therapyKiller cellsSpecific therapyClinical trialsT cellsDisease processDiabetes therapyMultifactorial diseaseCell pathwaysMultiple cell typesDiabetesT1DLymphocytesTherapyMonocytesDiseaseSuitable targetCell typesThe 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
Combined antibody therapy for type 1 diabetes (107.2)
Hu C, Ding H, Wong F, Wen L. Combined antibody therapy for type 1 diabetes (107.2). The Journal Of Immunology 2011, 186: 107.2-107.2. DOI: 10.4049/jimmunol.186.supp.107.2.Peer-Reviewed Original ResearchType 1 diabetesNOD miceB cellsBeneficial effectsTransgenic NOD miceDevelopment of T1D.CD4 T cellsAnti-CD3 treatmentNovel therapeutic approachesOral toleranceDiabetes preventionIL-10Antibody therapyAutoimmune diseasesPeyer's patchesT cellsTherapeutic approachesCombination treatmentMonoclonal antibodiesMiceIndividual antibodiesTregsAntibodiesCD20T1D.
2010
To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes
Wong F, Hu C, Xiang Y, Wen L. To B or not to B—pathogenic and regulatory B cells in autoimmune diabetes. Current Opinion In Immunology 2010, 22: 723-731. PMID: 21050736, DOI: 10.1016/j.coi.2010.10.002.Peer-Reviewed Original Research
2009
Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases
Hu C, Wong F, Wen L. Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases. Clinical & Experimental Immunology 2009, 157: 181-190. PMID: 19604257, PMCID: PMC2730843, DOI: 10.1111/j.1365-2249.2009.03977.x.Peer-Reviewed Original ResearchConceptsB cell-directed therapiesCell-directed therapiesAutoimmune diseasesB cellsT cellsRegulatory B cell subsetsOrgan-specific autoimmune diseasesTranslational Mini‐Review SeriesAmeliorate autoimmune diseaseRegulatory B cellsAnti-inflammatory cytokinesB cell subsetsAutoreactive B cellsMini‐Review SeriesProinflammatory cytokinesSpecific autoantigensCell subsetsTherapyDiseaseVicious cycleCytokinesCellsAutoantibodiesAutoantigensPathogenesisCellular 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
Autoimmune syndrome after induction of neonatal tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity
Merino J, Schurmans S, Wen L, Brighouse G, Luzuy S, Lambert P. Autoimmune syndrome after induction of neonatal tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity. Clinical & Experimental Immunology 2008, 79: 273-278. PMID: 1968797, PMCID: PMC1534764, DOI: 10.1111/j.1365-2249.1990.tb05190.x.Peer-Reviewed Original ResearchConceptsDonor T cellsF1 donor B cellsDonor B cellsT cell subsetsAutoimmune syndromeF1 cellsT cellsNeonatal toleranceCell subsetsSpleen cellsNewborn miceB cellsBALB/c newborn miceMature donor T cellsDifferent T cell subsetsAutoreactive B cell clonesBALB/c miceLupus-like syndromeDeposits of immunoglobulinsF1 spleen cellsInduction of autoimmunityAnti-Sm antibodiesB cell clonesCTL alloreactivityTolerant mice
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 mechanismsAnti-CD20 Therapy in NOD Model of Type 1 Diabetes (131.26)
Hu C, Rodriguez D, Du W, Ahuja A, Wong F, Shlomchik M, Wen L. Anti-CD20 Therapy in NOD Model of Type 1 Diabetes (131.26). The Journal Of Immunology 2007, 178: s242-s242. DOI: 10.4049/jimmunol.178.supp.131.26.Peer-Reviewed Original ResearchTransgenic NOD miceB cellsNOD miceT cellsHuman CD20Pre-diabetic stageB-cell depletionRegulatory T cellsOnset of diabetesPathogenesis of T1DTGF-β productionType 1 diabetesAbstract B cellsCD20 therapyImportant APCsDiabetes onsetT1D patientsNOD modelAutoimmune diseasesCell depletionClinical trialsPreclinical studiesParticular therapyHuman studiesCD20
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
2004
Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse
Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CA, Shlomchik MJ. Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse. Diabetes 2004, 53: 2581-2587. PMID: 15448087, DOI: 10.2337/diabetes.53.10.2581.Peer-Reviewed Original ResearchConceptsB cell-deficient miceAntigen-presenting functionType 1 diabetesB cellsNOD miceNormal NOD miceIncidence of diabetesDevelopment of diabetesT cell repertoireB cell repertoireAntigen presentationDiabetesAntibody productionMiceImmunoglobulin transgenesReduced abilityCell surfaceInsulitisAutoantibodiesIncidenceImmunoglobulinAntibodies