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
2022
Obesity aggravates contact hypersensitivity reaction in mice
Majewska‐Szczepanik M, Kowalczyk P, Marcińska K, Strzępa A, Lis GJ, Wong FS, Szczepanik M, Wen L. Obesity aggravates contact hypersensitivity reaction in mice. Contact Dermatitis 2022, 87: 28-39. PMID: 35234303, PMCID: PMC9949724, DOI: 10.1111/cod.14088.Peer-Reviewed Original ResearchConceptsContact hypersensitivityFecal microbiota transplantationQuantitative polymerase chain reactionIL-17AObese miceEnhanced contact hypersensitivityGut microbiota dysbiosisLow-grade inflammationContact hypersensitivity reactionInfluence of obesityInflammatory skin diseaseT helper 1Antigen-specific responsesHigh-fat dietSubcutaneous adipose tissueProinflammatory CD4Proinflammatory milieuCytokine profileMicrobiota dysbiosisDendritic cellsLymph nodesMicrobiota transplantationHelper 1Hypersensitivity reactionsImmune cells
2021
IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice
Huang J, Tan Q, Tai N, Pearson JA, Li Y, Chao C, Zhang L, Peng J, Xing Y, Zhang L, Hu Y, Zhou Z, Wong FS, Wen L. IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice. Frontiers In Immunology 2021, 12: 702955. PMID: 34394099, PMCID: PMC8362616, DOI: 10.3389/fimmu.2021.702955.Peer-Reviewed Original ResearchConceptsNOD miceProportion of neutrophilsT cellsGut microbiotaDiabetes developmentT cell-mediated destructionT cell receptor transgenicType 1 diabetes developmentAccelerated diabetes developmentInhibition of diabetesModulation of InnatePathogenicity of CD4Cell-mediated destructionAdaptive immune cellsObese diabetic miceT regulatory (Treg) cellsDevelopment of diabetesPrevention of diabetesActivation of CD4Modulation of neutrophilsType 1 diabetesGut microbiota compositionInsulin-producing β-cellsSevere insulitisSpontaneous diabetesToll-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
2015
NLRP3 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
2014
Toll-Like Receptor 3 Is Critical for Coxsackievirus B4-Induced Type 1 Diabetes in Female NOD Mice
McCall K, Thuma J, Courreges M, Benencia F, James C, Malgor R, Kantake N, Mudd W, Denlinger N, Nolan B, Wen L, Schwartz F. Toll-Like Receptor 3 Is Critical for Coxsackievirus B4-Induced Type 1 Diabetes in Female NOD Mice. Endocrinology 2014, 156: 453-461. PMID: 25422874, PMCID: PMC4298321, DOI: 10.1210/en.2013-2006.Peer-Reviewed Original ResearchConceptsToll-like receptor 3TLR3 knockout miceWild-type miceNOD miceKnockout miceRole of TLR3Receptor 3Type 1 diabetes mellitusFemale NOD miceProne NOD miceNonobese diabetic (NOD) miceIncidence of diabetesType 1 diabetesViral double-stranded RNAGroup B coxsackievirusesHuman T1DMDiabetes mellitusDiabetic miceMouse modelT1DMTLR3 knockoutUninfected counterpartsUninfected animalsB coxsackievirusesInsulitisIRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice
Tan Q, Majewska-Szczepanik M, Zhang X, Szczepanik M, Zhou Z, Wong FS, Wen L. IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice. Diabetes 2014, 63: 2761-2775. PMID: 24696448, PMCID: PMC4113073, DOI: 10.2337/db13-1504.Peer-Reviewed Original ResearchConceptsDiabetogenic T cellsNOD miceRapid progressionT cellsInterleukin-1 receptor-associated kinase MOrgan-specific autoimmune diseasesType 1 diabetes mellitusAnti-insulin autoantibodiesImmunodeficient NOD miceImpaired glucose toleranceAntigen-presenting functionNonobese diabetic (NOD) miceToll-like receptor pathwayAntigen-presenting cellsEnhanced activationType 1 diabetesInnate immune pathwaysIRAK-M deficiencyInnate immune processesInsulin-secreting pancreatic β-cellsPancreatic β-cellsSevere insulitisAutoimmune diabetesDendritic cellsDiabetes mellitusLong term effect of gut microbiota transfer on diabetes development
Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. Journal Of Autoimmunity 2014, 53: 85-94. PMID: 24767831, PMCID: PMC4361177, DOI: 10.1016/j.jaut.2014.03.005.Peer-Reviewed Original ResearchConceptsNOD miceGut microbiotaWild-type NOD miceNon-obese diabetic (NOD) miceGut microbiomeMyD88-deficient miceMucosal immune systemOnset of diabetesCD8αβ T cellsType 1 diabetesGut microbiota transferWeeks of ageAutoimmune diabetesT1D developmentDiabetes developmentDiabetic miceMicrobiota transferT cellsLamina propriaLong-term effectsProbiotic treatmentImmune systemLarge intestineDiabetesMice
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
TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes
Dong B, Qi D, Yang L, Huang Y, Xiao X, Tai N, Wen L, Wong F. TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes. AJP Heart And Circulatory Physiology 2012, 303: h732-h742. PMID: 22842069, PMCID: PMC3468457, DOI: 10.1152/ajpheart.00948.2011.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBlood GlucoseCell LineDiabetes Mellitus, Type 1Diabetic CardiomyopathiesDisease Models, AnimalFatty Acids, NonesterifiedJNK Mitogen-Activated Protein KinasesLipid MetabolismLipoprotein LipaseMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMyeloid Differentiation Factor 88MyocardiumMyocytes, CardiacOleic AcidP38 Mitogen-Activated Protein KinasesPhosphorylationRatsRNA InterferenceTime FactorsToll-Like Receptor 4TriglyceridesConceptsDiabetic heart diseaseType 1 diabetesHeart diseaseNOD animalsLipoprotein lipaseLipid accumulationNonobese diabetic (NOD) mouse modelLeft ventricular developed pressureCardiac fatty acid metabolismMyeloid differentiation primary response geneCardiac lipid accumulationControl nondiabetic miceGreater ejection fractionRole of TLR4Nonobese diabetic (NOD) miceOnset of diabetesVentricular developed pressureDevelopment of diabetesToll-like receptorsGreater fractional shorteningDiabetic mouse modelPlasma triglyceride levelsWild-type NODLower triglyceride accumulationCellular lipid accumulation
2010
Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens
Burton O, Gibbs S, Miller N, Jones F, Wen L, Dunne D, Cooke A, Zaccone P. Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens. European Journal Of Immunology 2010, 40: 2221-2229. PMID: 20480503, DOI: 10.1002/eji.200939998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, HelminthCD4-Positive T-LymphocytesCells, CulturedFemaleForkhead Transcription FactorsGalectin 3Helminth ProteinsHost-Pathogen InteractionsImmunomodulationLectins, C-TypeMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMinor Histocompatibility AntigensReceptors, Cell SurfaceSchistosoma mansoniToll-Like Receptor 2Transforming Growth Factor betaConceptsS. mansoni soluble egg antigenSchistosoma mansoni antigensT cellsFoxp3 expressionImportance of TLR2S. mansoni antigensSurface-bound TGFTLR2 ligand stimulationT cell secretionAccessory cell interactionsNOD miceTh2 responsesEgg antigenImmunomodulatory effectsT lymphocytesAbsence of APCC-type lectinBioactive TGFGalectin-3AntigenTGFTLR2Cell interactionsCellsLigand stimulation
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 3DiabetesMiceTLR3DiseaseImmunityReceptorsInnate 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
1998
The expression in vivo of a second isoform of pT alpha: implications for the mechanism of pT alpha action.
Barber D, Passoni L, Wen L, Geng L, Hayday A. The expression in vivo of a second isoform of pT alpha: implications for the mechanism of pT alpha action. The Journal Of Immunology 1998, 161: 11-6. PMID: 9647201, DOI: 10.4049/jimmunol.161.1.11.Peer-Reviewed Original ResearchPrimary 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 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 receptorInfectionMiceGerminal 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
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