2019
Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions
Pearson JA, Tai N, Ekanayake-Alper DK, Peng J, Hu Y, Hager K, Compton S, Wong FS, Smith PC, Wen L. Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions. Frontiers In Immunology 2019, 10: 2654. PMID: 31798584, PMCID: PMC6863139, DOI: 10.3389/fimmu.2019.02654.Peer-Reviewed Original ResearchConceptsExpansion of TregsNOD miceT cellsMNV4 infectionMucosal immunityNon-obese diabetic (NOD) mouse modelGerm-free NOD miceFirmicutes/Bacteroidetes ratioProinflammatory T cellsRole of norovirusesTuft cell markersDevelopment of T1DInflammatory T cellsCommon enteric virusesB cell subsetsDiabetic mouse modelImmune cell functionType 1 diabetes susceptibilityEnteric virusesNaïve splenocytesT1D protectionTreg numbersImmunological changesMucosal antibodiesT1D development
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 bacteriaNLRP3 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
2013
TLR9 Deficiency Promotes CD73 Expression in T Cells and Diabetes Protection in Nonobese Diabetic Mice
Tai N, Wong FS, Wen L. TLR9 Deficiency Promotes CD73 Expression in T Cells and Diabetes Protection in Nonobese Diabetic Mice. The Journal Of Immunology 2013, 191: 2926-2937. PMID: 23956420, PMCID: PMC3788667, DOI: 10.4049/jimmunol.1300547.Peer-Reviewed Original ResearchConceptsNOD miceCD73 expressionT cellsTLR9 deficiencyDiabetes developmentImmune cellsAnti-inflammatory cytokine productionImproved β-cell functionImportant immune regulatory roleStrong immunosuppressive functionNonobese diabetic (NOD) miceIncidence of diabetesNOD mouse modelPeripheral lymphoid tissuesImmune regulatory roleType 1 diabetesΒ-cell functionNew therapeutic strategiesElevated frequencyNOD backgroundDiabetes protectionDiabetic miceImmunosuppressive functionProinflammatory cytokinesCytokine productionRole of IRAK-M in Alcohol Induced Liver Injury
Wang Y, Hu Y, Chao C, Yuksel M, Colle I, Flavell RA, Ma Y, Yan H, Wen L. Role of IRAK-M in Alcohol Induced Liver Injury. PLOS ONE 2013, 8: e57085. PMID: 23437317, PMCID: PMC3578822, DOI: 10.1371/journal.pone.0057085.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticCD8-Positive T-LymphocytesDisease Models, AnimalForkhead Transcription FactorsGenome-Wide Association StudyImmunophenotypingInterferon-gammaInterleukin-1 Receptor-Associated KinasesIntestinal MucosaIntestinesLiver Diseases, AlcoholicMetagenomeMiceMice, KnockoutPermeabilityPhagocytosisPhysical Chromosome MappingPolymorphism, Single NucleotideT-LymphocytesT-Lymphocytes, RegulatoryConceptsAbsence of IRAKAlcohol-induced liver injuryLiver injuryToll-like receptorsInnate immunityAlanine transaminaseAlcohol-induced liver injury modelsInterleukin receptor-associated kinaseAltered gut bacteriaHigher alanine transaminaseNumbers of IFNγWorse liver injuryAlcoholic liver injuryInduced liver injuryImmune cell infiltrationAdaptive immune responsesRole of IRAKLiver injury modelReceptor-associated kinaseGut permeabilityAcute insultB6 miceLiver damageCell infiltrationInjury model
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 types
2011
IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice
Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L. IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clinical Immunology 2011, 139: 336-349. PMID: 21458378, DOI: 10.1016/j.clim.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenDendritic CellsDiabetes Mellitus, Type 1Disease Models, AnimalFemaleHLA-DQ AntigensHumansImmune ToleranceImmunophenotypingInsulin-Secreting CellsInterleukin-10Lymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred NODMice, SCIDMice, TransgenicSpecific Pathogen-Free OrganismsT-LymphocytesConceptsRIP-B7.1 miceAutoimmune diabetesIL-10IL-10-treated DCIL-12/23 p40T cell toleranceT cell proliferationDifferent animal modelsNew therapeutic interventionsSpontaneous diabetesRegulatory cellsDendritic cellsImmune toleranceCostimulatory moleculesIL-6IL-4T cellsAnimal modelsCell toleranceTherapeutic interventionsDiabetesCell proliferationT1D.MiceCells
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
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
2008
Elevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease
WEN L, PEAKMAN M, MIELI-VERGANI G, VERGANI D. Elevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease. Clinical & Experimental Immunology 2008, 89: 78-82. PMID: 1385768, PMCID: PMC1554410, DOI: 10.1111/j.1365-2249.1992.tb06881.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAntigens, CDAutoimmune DiseasesChildCholangitis, SclerosingFemaleFlow CytometryFluorescent Antibody TechniqueHepatitis, ChronicHistocompatibility AntigensHLA-DR AntigensHumansLeukocyte Common AntigensLiver DiseasesMaleReceptors, Antigen, T-Cell, gamma-deltaReceptors, Interleukin-2T-LymphocytesConceptsPrimary sclerosing cholangitisGroup of patientsTCR gamma deltaT cellsAI-CAHLiver diseaseHLA-DRPeripheral bloodAutoimmune chronic active hepatitisAutoimmune chronic liver diseaseMemory cell marker CD45ROActivation markers HLA-DRΓδ T cell receptorAbsolute numberAutoimmune liver diseaseChronic active hepatitisChronic liver diseaseMarkers HLA-DRGamma delta T cell receptor (TCR) heterodimerIL-2 receptorT cell receptorT cell receptor heterodimerLevels of gammaActive hepatitisSclerosing cholangitisThe human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation
WONG F, HIBBERD M, WEN L, MILLWARD B, DEMAINF A. The human T cell receptor Vβ repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation. Clinical & Experimental Immunology 2008, 92: 361-366. PMID: 8387412, PMCID: PMC1554814, DOI: 10.1111/j.1365-2249.1993.tb03405.x.Peer-Reviewed Original ResearchConceptsT cellsMitogen stimulationT cell antigen receptorPolymerase chain reactionT cell receptor Vβ repertoireFlow cytometryNormal peripheral blood lymphocytesMitogen-stimulated T cellsPeripheral blood lymphocytesTCR gene usagePeripheral T cellsT cell linesVβ repertoireUnstimulated T cellsBeta repertoireBlood lymphocytesHealthy individualsPCR methodBeta 6Cell antigen receptorGene usageAntigen receptorBeta 2Beta 5Chain reactionAutoimmune 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
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
2003
Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans
Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans. International Immunology 2003, 15: 1035-1044. PMID: 12917255, DOI: 10.1093/intimm/dxg103.Peer-Reviewed Original ResearchConceptsCo-stimulatory molecules B7-1Incidence of diabetesTransgenic miceB7-1Autoimmune diabetesHLA-DQ8HLA-DR3T cellsBeta cellsBeta-cell toxin streptozotocinHLA class II associationsDQ8 transgenic micePresence of DR3HLA transgenic miceAntibody-mediated depletionPathogenesis of T1D.Class II associationsHLA class IIWhole-body irradiationPancreatic beta cellsNon-specific activationSpontaneous diabetesToxin streptozotocinDiabetogenic potentialSTZ treatmentCritical roles of CD30/CD30L interactions in murine autoimmune diabetes
CHAKRABARTY S, NAGATA M, YASUDA H, WEN L, NAKAYAMA M, CHOWDHURY S, YAMADA K, JIN Z, KOTANI R, MORIYAMA H, SHIMOZATO O, YAGITA H, YOKONO K. Critical roles of CD30/CD30L interactions in murine autoimmune diabetes. Clinical & Experimental Immunology 2003, 133: 318-325. PMID: 12930356, PMCID: PMC1808783, DOI: 10.1046/j.1365-2249.2003.02223.x.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalAutoimmune DiseasesCD30 LigandCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, ExperimentalFemaleIslets of LangerhansKi-1 AntigenMaleMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDT-LymphocytesT-Lymphocytes, CytotoxicConceptsCD30/CD30L interactionIslet-specific CD4NOD miceDevelopment of diabetesT cell linesAutoimmune diabetesDiabetic NOD miceSpontaneous autoimmune diabetesPancreatic lymph nodesYoung NOD miceNOD-SCID miceT cell proliferationCD30/CD30LTumor necrosis factor receptorWeeks of ageCell linesNecrosis factor receptorMurine autoimmuneIslet antigensSpontaneous diabetesAdoptive transferLymph nodesEffector phaseT cellsSpleen cells
2001
Report From the 1st International NOD Mouse T-Cell Workshop and the Follow-Up Mini-Workshop
Kaufman D, Tisch R, Sarvetnick N, Chatenoud L, Harrison L, Haskins K, Quinn A, Sercarz E, Singh B, von Herrath M, Wegmann D, Wen L, Zekzer D. Report From the 1st International NOD Mouse T-Cell Workshop and the Follow-Up Mini-Workshop. Diabetes 2001, 50: 2459-2463. PMID: 11679422, DOI: 10.2337/diabetes.50.11.2459.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAnimalsAutoimmune DiseasesAutoimmunityHumansMiceMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesConceptsΓδ 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 betaLupusDiseaseMiceCellsErythematosusHypergammaglobulinemiaAutoantibodiesCD4AutoimmunityKidneyGerminal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.
Wen L, Pao W, Wong FS, Peng Q, Craft J, Zheng B, Kelsoe G, Dianda L, Owen MJ, Hayday AC. Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells. Journal Of Experimental Medicine 1996, 183: 2271-2282. PMID: 8642336, PMCID: PMC2192585, DOI: 10.1084/jem.183.5.2271.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesClone CellsFlow CytometryGerminal CenterHumansImmunoglobulin Class SwitchingImmunoglobulin EImmunoglobulin GLupus Erythematosus, SystemicLymphocyte DepletionMiceMice, Inbred NODMice, Inbred StrainsMice, KnockoutMice, SCIDReceptors, Antigen, T-Cell, alpha-betaSpleenT-LymphocytesConceptsSystemic lupus erythematosusBeta T cellsAlpha/beta T cellsGamma/delta T cellsDelta T cellsT cell helpT cellsT cell receptorCell helpT cell-mediated conditionsHuman systemic lupus erythematosusSevere combined immunodeficient (SCID) miceDevelopment of autoantibodiesCombined Immunodeficient MiceT-cell immunodeficiencyClass-switched antibodiesB cell collaborationGerminal center formationLupus erythematosusAutoantibody productionLymphoid folliclesImmunoglobulin class switchingIgE synthesisAlpha/betaCell immunodeficiency