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
2016
Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production
Majewska-Szczepanik M, Askenase PW, Lobo FM, Marcińska K, Wen L, Szczepanik M. Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production. Journal Of Allergy And Clinical Immunology 2016, 138: 262-273.e6. PMID: 26810716, PMCID: PMC5278675, DOI: 10.1016/j.jaci.2015.11.018.Peer-Reviewed Original ResearchConceptsSubcutaneous allergen-specific immunotherapyOVA-specific IgEEpicutaneous immunizationAllergen-specific immunotherapyAntigen-specific mannerT cell receptorAllergic diseasesToll-like receptor 9 agonistMyeloid differentiation primary response 88Differentiation primary response 88Course of allergyIL-17A dependentTolerability of immunotherapyLong-term remissionTH1/TH17 cytokinesReceptor 9 agonistAdoptive cell transferEosinophil peroxidase activityEpicutaneous treatmentRegulatory cellsTh17 cytokinesAtopic dermatitisIL-10IgG2a productionIgE synthesis
2014
IRAK-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 mellitus
2012
Epicutaneous 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
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 mechanismsCD86 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
2006
TGF-β signaling is required for the function of insulin-reactive T regulatory cells
Du W, Wong FS, Li MO, Peng J, Qi H, Flavell RA, Sherwin R, Wen L. TGF-β signaling is required for the function of insulin-reactive T regulatory cells. Journal Of Clinical Investigation 2006, 116: 1360-1370. PMID: 16670772, PMCID: PMC1451206, DOI: 10.1172/jci27030.Peer-Reviewed Original ResearchConceptsT cellsNOD miceRegulatory cellsDominant negative TGF-beta receptor type IITransgenic miceTCR transgenic T cellsTGF-beta receptor type IIDiabetic NOD miceDiabetogenic spleen cellsDiabetogenic T cellsTCR transgenic miceTransgenic T cellsReceptor type IIBDC2.5 miceAdoptive transferTGF-beta signalingSpleen cellsParacrine mannerGranule antigensAutocrine mannerSuppressive propertiesDiabetesMiceTarget cellsSpontaneous development
2001
Type 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
2000
In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes
Wen L, Wong F, Tang J, Chen N, Altieri M, David C, Flavell R, Sherwin R. In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes. Journal Of Experimental Medicine 2000, 191: 97-104. PMID: 10620608, PMCID: PMC2195792, DOI: 10.1084/jem.191.1.97.Peer-Reviewed Original ResearchConceptsClass II moleculesMHC class II moleculesGlutamic acid decarboxylaseRat insulin promoterSpontaneous diabetesB7-1T cellsBeta cellsMouse MHC class II moleculesTransgenic miceHuman histocompatibility leukocyte antigenHuman type 1 diabetesMajor histocompatibility complex (MHC) class II moleculesCostimulatory molecules B7-1Human MHC class II moleculesVivo evidenceHistocompatibility leukocyte antigenDevelopment of diabetesType 1 diabetesMHC class IIC57BL/6 transgenic miceMurine MHC class IIPancreatic beta cellsVivo experimental evidenceDiabetogenic role
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
Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse
Zekzer D, Wong F, Wen L, Altieri M, Gurlo T, von Grafenstein H, Sherwin R. Inhibition of Diabetes by an Insulin-Reactive CD4 T-Cell Clone in the Nonobese Diabetic Mouse. Diabetes 1997, 46: 1124-1132. PMID: 9200646, DOI: 10.2337/diab.46.7.1124.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCattleCD4 AntigensCell Adhesion MoleculesClone CellsCytokinesDiabetes Mellitus, Type 2Disease Models, AnimalDose-Response Relationship, DrugFemaleFlow CytometryInsulinMiceMice, Inbred NODPolymerase Chain ReactionRatsReceptors, Antigen, T-Cell, alpha-betaRNASpecific Pathogen-Free OrganismsTh1 CellsConceptsNOD miceDiabetic splenocytesIslet supernatantAdoptive transferDiabetic miceCD4 T-cell clonesInhibition of diabetesInjection of splenocytesPancreatic lymph nodesNonobese diabetic (NOD) miceAnti-transforming growthT cell clonesTh1 cell linesT cell receptorNOD isletsNOD splenocytesSpontaneous diabetesInsulin therapyLymph nodesAntibody treatmentTh1 cellsProtective effectDiabetesB chain peptideSplenocytes
1996
CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. Journal Of Experimental Medicine 1996, 183: 67-76. PMID: 8551245, PMCID: PMC2192404, DOI: 10.1084/jem.183.1.67.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenBase SequenceCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesClone CellsCytokinesDiabetes Mellitus, Type 2FemaleImmunohistochemistryImmunotherapy, AdoptiveInsulinIslets of LangerhansLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDMolecular Sequence DataPancreasPerforinPore Forming Cytotoxic ProteinsPromoter Regions, GeneticConceptsT cell linesNOD miceT cellsCD8 T cell linesCD8 T cell clonesNonobese diabetic (NOD) miceCB17 SCID miceCD4 T cellsPathogenesis of diabetesT cell clonesCell linesIslets of LangerhansT cell antigen receptorNOD isletsCD4 cellsLymphocytic infiltrateNOD-SCIDDiabetic miceDiabetic isletsFemale NODRapid onsetCell antigen receptorH-2KdAntigen receptorMice