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 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
Circadian Rhythm Modulation of Microbes During Health and Infection
Pearson JA, Voisey AC, Boest-Bjerg K, Wong FS, Wen L. Circadian Rhythm Modulation of Microbes During Health and Infection. Frontiers In Microbiology 2021, 12: 721004. PMID: 34512600, PMCID: PMC8430216, DOI: 10.3389/fmicb.2021.721004.Peer-Reviewed Original ResearchGut bacteriaProtective immune responseBeneficial therapeutic responseCircadian rhythm modulationVaccination responseTherapeutic responseTherapeutic administrationImmune responseTherapeutic successCircadian rhythm effectsHost immunityRhythm modulationAdverse effectsInfectionDay-dependent changesAdministration strategiesAltered susceptibilityRhythm effectsCircadian rhythmHealthCircadian modulationVirusOptimal timePhysiological processesResponseInflammasomes and Type 1 Diabetes
Pearson JA, Wong FS, Wen L. Inflammasomes and Type 1 Diabetes. Frontiers In Immunology 2021, 12: 686956. PMID: 34177937, PMCID: PMC8219953, DOI: 10.3389/fimmu.2021.686956.Peer-Reviewed Original ResearchConceptsType 1 diabetesMultiprotein complexesEnhanced toleranceMicrobial ligandsIslet autoantibody developmentImmune responseGenetic associationMicrobial stimulationAvailable inhibitorsImportant modulatorType 1 diabetes susceptibilityPathwayDiabetes susceptibilityAutoimmune processMicrobiota compositionAutoantibody developmentMicrobiotaAnimal modelsInflammasomeActivationGenetic riskType 1DiabetesHumansRole
2020
Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes
Huang J, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Guo K, Wong FS, Zhou Z, Wen L. Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes. The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa590. PMID: 32860693, PMCID: PMC7549925, DOI: 10.1210/clinem/dgaa590.Peer-Reviewed Original ResearchConceptsIgA-bound bacteriaType 1 diabetesHealthy control individualsIgA immune responseControl individualsIgA immunityAutoantibody titersIgA concentrationsImmune responseType 1 diabetes patientsΒ-cell autoimmunityLonger disease durationSerum IgA concentrationNovel therapeutic targetEnzyme-linked immunosorbentDisease durationIgA levelsDiabetes patientsDiabetes displayGut homeostasisBlood samplesOral cavityTherapeutic targetDiabetesHost immunityGut microbial metabolites alter IgA immunity in type 1 diabetes
Huang J, Pearson JA, Peng J, Hu Y, Sha S, Xing Y, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Wong F, Zhou Z, Wen L. Gut microbial metabolites alter IgA immunity in type 1 diabetes. JCI Insight 2020, 5 PMID: 32298241, PMCID: PMC7259536, DOI: 10.1172/jci.insight.135718.Peer-Reviewed Original ResearchConceptsType 1 diabetesGut microbiotaNOD miceImmune responseGerm-free NOD miceIgA immune responseIgA-mediated immunityHealthy control subjectsPotential therapeutic agentShort-chain fatty acid productionIgA immunityT1D preventionIgA responsesControl subjectsDecreased severityT1DTherapeutic agentsFunctional effectsMicrobiotaDiabetesPatientsUnderlying mechanismMiceImmunitySCFA
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
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 modelTLR3Cellular 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
Toll‐Like Receptors and Diabetes
Wong F, Wen L. Toll‐Like Receptors and Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 123-132. PMID: 19120280, DOI: 10.1196/annals.1447.063.Peer-Reviewed Original ResearchConceptsToll-like receptorsAntigen-presenting cellsType 1 interferonAdaptive immune systemRegulatory cellsAutoimmune responseInflammatory cytokinesMore specific responsesIFN-alphaImmune responseEndogenous ligandImmune systemMolecular patternsInfectionMicrobial infectionsReceptorsInterferonEndogenous stimuliDirect effectCellular stressSpecific responsesCellsResponseAutoimmunityDiabetesInnate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008, 455: 1109-1113. PMID: 18806780, PMCID: PMC2574766, DOI: 10.1038/nature07336.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1FemaleImmunity, InnateInterferon-gammaIntestinesIslets of LangerhansMaleMiceMice, Inbred NODMice, KnockoutMice, SCIDMolecular Sequence DataMyeloid Differentiation Factor 88PhylogenySpecific Pathogen-Free OrganismsTime FactorsConceptsType 1 diabetesNOD miceInnate immunityRapid innate immune responseDevelopment of diabetesNormal human gutInnate immune responseAdaptor protein MyD88Autoimmune diabetesTherapeutic optionsImmune responseNegative miceIntestinal microbiotaProtein MyD88DiabetesMiceGut microbesImmunityHuman gutMicrobial productsMyD88Influence predispositionIncidence
2007
CD86 Has Sustained Costimulatory Effects on CD8 T Cells
Thomas IJ, de Marquesini L, Ravanan R, Smith RM, Guerder S, Flavell RA, Wraith DC, Wen L, Wong FS. CD86 Has Sustained Costimulatory Effects on CD8 T Cells. The Journal Of Immunology 2007, 179: 5936-5946. PMID: 17947667, PMCID: PMC2629533, DOI: 10.4049/jimmunol.179.9.5936.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-1 AntigenB7-2 AntigenCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationCells, CulturedCytokinesDiabetes MellitusGene Expression RegulationHealthHumansIslets of Langerhans TransplantationMiceMice, TransgenicPromoter Regions, GeneticRatsReceptor, InsulinSurvival RateTime FactorsTransgenesConceptsCD8 T cellsT cellsT cell activationCD86 costimulationCell activationCytotoxic T-cell activationTransfer of diabetesOld NOD miceInhibitory molecule expressionRat insulin promoterGreater sustained activityNOD isletsRecurrent diabetesNOD miceDiabetes onsetDiabetic miceCostimulatory moleculesCTLA-4Cytokine secretionMolecule expressionCostimulatory effectImmune responseCD80CD86CD80 costimulation
2001
The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model
Wen L, Chen N, Tang J, Sherwin R, Wong F. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. Journal Of Clinical Investigation 2001, 107: 871-880. PMID: 11285306, PMCID: PMC199575, DOI: 10.1172/jci11708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, Type 1Disease Models, AnimalFemaleGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHLA-DR4 AntigenIncidenceInsulinMaleMiceMice, Inbred C57BLMice, TransgenicMicrosatellite RepeatsPancreasSialadenitisSpleenTh2 CellsTransgenesConceptsMHC class II moleculesSpontaneous diabetesClass II moleculesTransgenic miceT cellsHLA-DQ8Diabetogenic effectMouse MHC class II moleculesHLA-DR transgenic miceTh2-like immune responsesHuman type 1 diabetesAutoreactive T cellsDouble transgenic miceType 1 diabetesC57BL/6 transgenic miceTh2-like phenotypePancreatic beta cellsExpression of DR4DQ8 allelesDiabetes developmentCostimulatory moleculesHLA-DQImmune responseBeta cellsDiabetesType 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model
Abraham R, Wen L, Marietta E, David C. Type 1 Diabetes-Predisposing MHC Alleles Influence the Selection of Glutamic Acid Decarboxylase (GAD) 65-Specific T Cells in a Transgenic Model. The Journal Of Immunology 2001, 166: 1370-1379. PMID: 11145722, DOI: 10.4049/jimmunol.166.2.1370.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceAnimalsAntibody SpecificityCells, CulturedCytokinesDiabetes Mellitus, Type 1Disease Models, AnimalEpitopes, T-LymphocyteGenes, MHC Class IIGenetic Predisposition to DiseaseGlutamate DecarboxylaseHLA-DQ AntigensHLA-DR3 AntigenHumansImmunophenotypingIslets of LangerhansIsoenzymesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicMolecular Sequence DataRatsT-Lymphocyte SubsetsConceptsGlutamic acid decarboxylaseGAD 65T cellsDQ8 miceMixed Th1/Th2 cytokine profileEndogenous MHC class IISpontaneous T-cell reactivityTh1/Th2 cytokine profileGlutamic acid decarboxylase 65Self-reactive responsesT cell reactivityTh2 cytokine profileAutoantigen glutamic acid decarboxylase 65Type 1 diabetesMHC class IIDiabetes-associated genesCytokine profileIslet autoantigensHLA-DR3Immune toleranceHLA-DQ6Cell reactivitySelf-AgImmune responseHLA alleles
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
γδ T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells
Pao W, Wen L, Smith A, Gulbranson-Judge A, Zheng B, Kelsoe G, MacLennan I, Owen M, Hayday A. γδ T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells. Current Biology 1996, 6: 1317-1325. PMID: 8939571, DOI: 10.1016/s0960-9822(02)70718-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntibodies, ProtozoanB-LymphocytesCD4 AntigensCoccidiosisEimeriaGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorGerminal CenterImmunity, CellularImmunoglobulin GMiceMice, Mutant StrainsReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocytes, Helper-InducerConceptsGamma delta T cellsDelta T cellsT cell-B cell collaborationT cell helpT cell-deficient miceCell-deficient miceGamma delta cellsT cellsCell helpB cellsGerminal centersParasitic infectionsCell collaborationAlpha beta T cellsBeta T cellsT cell deficiencyDelta cellsDevelopment of autoimmunityAntibody levelsMycobacterial antigensCell deficiencyImmune responseAnatomical focusImmune systemAntibody specificity
1994
Lymphocyte proliferation in mice congenitally deficient in T-cell receptor alpha beta + cells.
Viney J, Dianda L, Roberts S, Wen L, Mallick C, Hayday A, Owen M. Lymphocyte proliferation in mice congenitally deficient in T-cell receptor alpha beta + cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 11948-11952. PMID: 7991563, PMCID: PMC45353, DOI: 10.1073/pnas.91.25.11948.Peer-Reviewed Original ResearchConceptsTCR gamma deltaTCR alpha betaGamma deltaAlpha betaT-cell receptor alpha betaT cell receptor expressionSurface activation markersAlpha mutant miceWild-type animalsActivation markersEnvironmental antigensLymphoid componentLymphocyte proliferationLymphoid organsLymphoid tissueReceptor expressionT cellsImmune responseMutant miceAbsolute numberMiceSubstantial proportionCell populationsPrimary regulatorBeta