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
2022
Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Yang ML, Connolly SE, Gee RJ, Lam TT, Kanyo J, Peng J, Guyer P, Syed F, Tse HM, Clarke SG, Clarke CF, James EA, Speake C, Evans-Molina C, Arvan P, Herold KC, Wen L, Mamula MJ. Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity. Diabetes 2022, 71: 1979-1993. PMID: 35730902, PMCID: PMC9450849, DOI: 10.2337/db21-0989.Peer-Reviewed Original ResearchConceptsType 1 diabetesNOD miceMurine type 1 diabetesHuman type 1 diabetesDecreased glucose-stimulated insulin secretionAnti-insulin autoimmunityPrediabetic NOD miceGlucose-stimulated insulin secretionOnset Type 1T cell responsesOnset of hyperglycemiaCirculation of patientsAutoreactive CD4Insulin ratioInsulin secretionDiabetesPancreatic isletsType 1Islet proteinsOxidative stressAutoimmunitySelect groupMiceCarbonyl modificationOnset
2021
Toll-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
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
2012
The 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 CD20Epicutaneous immunization with DNP‐BSA induces CD4+ CD25+ Treg cells that inhibit Tc1‐mediated CS
Majewska‐Szczepanik M, Zemelka‐Wiącek M, Ptak W, Wen L, Szczepanik M. Epicutaneous immunization with DNP‐BSA induces CD4+ CD25+ Treg cells that inhibit Tc1‐mediated CS. Immunology And Cell Biology 2012, 90: 784-795. PMID: 22290507, DOI: 10.1038/icb.2012.1.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCell CommunicationCell ProliferationCTLA-4 AntigenCytokinesDermatitis, ContactDinitrophenolsDose-Response Relationship, ImmunologicFemaleForkhead Transcription FactorsImmunizationInflammationInflammation MediatorsInterleukin-2 Receptor alpha SubunitLymphoid TissueMiceMice, Inbred BALB CPhenotypeReceptors, Antigen, T-Cell, alpha-betaSerum Albumin, BovineSkinT-Lymphocytes, CytotoxicT-Lymphocytes, RegulatoryConceptsEC immunizationLymph nodesContact sensitivityTreg cellsDNP-BSAEffector T cell responsesRegulatory T cellsT cell responsesSubcutaneous lymph nodesEpicutaneous immunizationInduces CD4Subsequent unresponsivenessIL-12Normal miceT cellsCS responsesImmunizationTranswell systemInhibited productionFlow cytometryProtein antigensCell proliferationLymphocytesCell contactSensitization
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 response
2006
Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility
Ge X, Piganelli J, Tse H, Bertera S, Mathews C, Trucco M, Wen L, Rudert W. Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility. Diabetes 2006, 55: 3455-3462. PMID: 17130492, DOI: 10.2337/db06-0680.Peer-Reviewed Original ResearchConceptsT cell responsesHLA moleculesCaucasian type 1 diabetic patientsCD4 T cell activityCD4 T cell linesCD4 T cell responsesType 1 diabetic patientsHLA class II allelesCertain HLA moleculesT cell activityType 1 diabetesClass II allelesT cell linesSpecific DRB1HLA-DQ8Diabetic patientsModulatory roleDisease riskDQ8Type 1DR4Diabetes susceptibilityPeptide occupancyPrimary genetic determinantGenetic determinants
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 receptorInfectionMice