2024
TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model
Pearson J, Hu Y, Peng J, Wong F, Wen L. TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model. Frontiers In Immunology 2024, 15: 1333967. PMID: 38482010, PMCID: PMC10935730, DOI: 10.3389/fimmu.2024.1333967.Peer-Reviewed Original ResearchConceptsToll-like receptor 5Antigen-presenting cellsDendritic cellsType 1 diabetesTLR5-deficientDC developmentCytokine secretionCD4<sup>+</sup> T cell proliferationPathogenesis of type 1 diabetesT cell responsesEnhanced cytokine secretionT cell proliferationWild-type miceSusceptibility to obesitySusceptibility to T1DProinflammatory cytokine secretionGut microbiotaSpontaneous T1DNOD miceAutoimmune diabetesNon-obeseHuman T1DReceptor 5Autoimmune diseasesHyper-secretion
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 rolePathogenesisLADADisease
2016
Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice
Hu Y, Jin P, Peng J, Zhang X, Wong FS, Wen L. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. Journal Of Autoimmunity 2016, 72: 47-56. PMID: 27178773, PMCID: PMC4958594, DOI: 10.1016/j.jaut.2016.05.001.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsType 1 diabetesAutoimmune diabetes developmentDiabetes developmentPregnant mothersEarly-life antibiotic exposureTolerogenic antigen-presenting cellsUntreated control miceInflammatory T cellsDifferent immunological responsesGut microbiota compositionDifferent immune responsesImportant environmental agentsGut bacterial compositionEarly time pointsNOD miceControl miceAutoimmune diseasesPrenatal exposureLymphoid organsAntibiotic exposureT cellsImmune responseImmunological responseNew therapies
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 bacteria
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
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
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 cycleCytokinesCellsAutoantibodiesAutoantigensPathogenesis
2008
The Role of Toll‐Like Receptors 3 and 9 in the Development of Autoimmune Diabetes in NOD Mice
Wong FS, Hu C, Zhang L, Du W, Alexopoulou L, Flavell RA, Wen L. The Role of Toll‐Like Receptors 3 and 9 in the Development of Autoimmune Diabetes in NOD Mice. Annals Of The New York Academy Of Sciences 2008, 1150: 146-148. PMID: 19120284, DOI: 10.1196/annals.1447.039.Peer-Reviewed Original ResearchConceptsToll-like receptorsNOD miceHeterozygous miceToll-like receptor 3Different Toll-like receptorsTLR3-deficient miceTLR9-deficient miceRole of TLR3Type 1 diabetesDifferent microbial stimuliNumber of receptorsAutoimmune diabetesSpontaneous diabetesAutoimmune diseasesMicrobial stimuliAdaptive immunityInnate responseInnate immunityReceptor 3DiabetesMiceTLR3DiseaseImmunityReceptors
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
2003
The study of HLA class II and autoimmune diabetes.
Wong F, Wen L. The study of HLA class II and autoimmune diabetes. 2003, 3: 1-15. PMID: 12558070, DOI: 10.2174/1566524033361591.Peer-Reviewed Original ResearchConceptsHLA moleculesTransgenic miceHuman leucocyte antigens DR3HLA transgenic miceCD4 T lymphocytesHLA class IIAntigen-specific cellsT cell epitopesMHC-peptide complexesPeptide-MHC complexesPutative autoantigenDiabetes mellitusAutoimmune diseasesAntigens DR3T lymphocytesCell epitopesClass IIPeptide antigensMajor histocompatibility complex class II lociMHC complexesDiseaseClass II lociDevelopment of reagentsMiceFurther studies
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
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
1997
γδ T-cell help in responses to pathogens and in the development of systemic autoimmunity
Wen L, Hayday A. γδ T-cell help in responses to pathogens and in the development of systemic autoimmunity. Immunologic Research 1997, 16: 229-241. PMID: 9379074, DOI: 10.1007/bf02786392.Peer-Reviewed Original ResearchConceptsΓδ T cellsT cell helpT cellsAutoimmune diseasesΑβ T cell-deficient miceT cell-deficient miceSelf-reactive IgGPhysiologic immune responseΑβ T cellsGerminal center formationAutoantibody formationSystemic autoimmunityImmune responseGerminal centersHealthy individualsB cellsProvision of helpDiseaseMiceCenter formationEnhanced levelsSignificant levelsAutoimmunityNewbornsSymptoms
1996
T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium.
Roberts S, Smith A, West A, Wen L, Findly R, Owen M, Hayday A. T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 11774-11779. PMID: 8876213, PMCID: PMC38134, DOI: 10.1073/pnas.93.21.11774.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD4-Positive T-LymphocytesCoccidiosisEimeriaGastrointestinal HemorrhageIntestinal DiseasesIntestinal MucosaIntestine, SmallLymph NodesLymphocyte TransfusionMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutPhenotypeReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesConceptsAlpha beta T cellsBeta T cellsT cellsGamma deltaT cell antigen receptorAlpha beta T-cell responsesT cell effector functionGamma delta T-cell antigen receptorsAlpha betaT cell responsesIntestinal damageProtective immunityAutoimmune diseasesEpithelial infectionDeficient miceEffector functionsEimeria vermiformisImmune systemCell responsesIntestinal epitheliumIntracellular protozoanWidespread infectionAntigen receptorInfectionMiceMurine lupus in the absence of alpha beta T cells.
Peng SL, Madaio MP, Hughes DP, Crispe IN, Owen MJ, Wen L, Hayday AC, Craft J. Murine lupus in the absence of alpha beta T cells. The Journal Of Immunology 1996, 156: 4041-9. PMID: 8621947, DOI: 10.4049/jimmunol.156.10.4041.Peer-Reviewed Original ResearchConceptsAlpha beta T cellsT cell-dependent mechanismBeta T cellsCell-dependent mechanismT cellsMurine lupusHuman systemic lupus erythematosusLupus-prone MRL miceSystemic lupus erythematosusSystemic autoimmune diseaseLupus erythematosusAutoimmune diseasesImmune depositsMRL miceAlpha betaLupusDiseaseMiceCellsErythematosusHypergammaglobulinemiaAutoantibodiesCD4AutoimmunityKidney
1994
Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes
Wong S, Wen L, Hibberd M, Millward A, Demaine A. Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes. Autoimmunity 1994, 18: 77-83. PMID: 7999959, DOI: 10.3109/08916939409014682.Peer-Reviewed Original ResearchConceptsTCRBV gene usageGene usageSemi-quantitative polymerase chain reaction (PCR) techniqueType INormal healthy controlsBeta gene usagePeripheral T cellsT cell clonesPolymerase chain reaction techniqueClinical onsetHLA-DR3Chain reaction techniqueAutoimmune diseasesTCR repertoireHealthy controlsT cellsPatientsClinical diagnosisMarked activationSequential samplesSignificant differencesDiseaseDiagnosisDR4Cytometry