2015
Gene therapy with neurogenin3, betacellulin and SOCS1 reverses diabetes in NOD mice
Li R, Buras E, Lee J, Liu R, Liu V, Espiritu C, Ozer K, Thompson B, Nally L, Yuan G, Oka K, Chang B, Samson S, Yechoor V, Chan L. Gene therapy with neurogenin3, betacellulin and SOCS1 reverses diabetes in NOD mice. Gene Therapy 2015, 22: 876-882. PMID: 26172077, PMCID: PMC4636470, DOI: 10.1038/gt.2015.62.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBasic Helix-Loop-Helix Transcription FactorsBetacellulinDiabetes Mellitus, ExperimentalFemaleGenetic TherapyImmunosuppression TherapyInsulinIslets of LangerhansIslets of Langerhans TransplantationLiverMiceMice, Inbred NODNerve Tissue ProteinsSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsConceptsSuppressor of cytokine signaling 1NOD miceGene therapyModel of autoimmune diabetesDiabetic miceLineage-defining transcription factorsGlucose-stimulated insulin secretionHelper-dependent adenovirusActivated T cellsLong-term reversal of diabetesRat insulin promoterReversal of diabetesShortage of donor isletsIslet neogenesisOverexpression suppressorIslet growth factorsNeo-isletsType 1 diabetesCytokine Signaling 1Transcription factorsTransfer diabetesNon-obeseTreated mice liverAutoimmune diabetesT cells
2012
Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c+ CD11b+ dendritic cells
Kriegel MA, Rathinam C, Flavell RA. Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c+ CD11b+ dendritic cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3457-3462. PMID: 22328150, PMCID: PMC3295274, DOI: 10.1073/pnas.1115308109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityCD11b AntigenCD11c AntigenCD4-Positive T-LymphocytesCell CountChemokine CCL2Dendritic CellsDiabetes Mellitus, Type 1FemaleGene Expression RegulationInsulinIslets of LangerhansLymph NodesMiceMice, Inbred NODMice, TransgenicPromoter Regions, GeneticRatsRecombinant Fusion ProteinsSelf ToleranceConceptsDendritic cellsType 1 diabetesCell infiltrateDiabetes developmentT cellsChemokine CCL2/MCPElevated IL-10 secretionPancreatic isletsCCL2/CCR2 axisCD80/CD86 expressionTransgenic NOD miceVivo transfer systemDendritic cell biologyImmune cell infiltratesIL-10 secretionNonobese diabetic (NOD) miceCCL2/MCPRat insulin promoterUnexpected beneficial roleHypoactive phenotypeLow CD40NOD backgroundPancreatic lymphAutoimmune diabetesNOD mice
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 costimulationDistinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes
Rajagopalan G, Mangalam A, Sen M, Kudva Y, David C. Distinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes. Autoimmunity 2007, 40: 489-496. PMID: 17966038, DOI: 10.1080/08916930701649836.Peer-Reviewed Original ResearchConceptsIncidence of diabetesPathogenesis of T1DRat insulin promoterTransgenic mouse modelMouse modelHLA-DQ8 transgenic miceMurine type 1 diabetesDouble transgenic mouse modelMHC class II associationsLocal inflammatory stimuliSpontaneous autoimmune diabetesT cell subsetsClass II associationsType 1 diabetesAutoimmune diabetesImmunogenic stimulusProinflammatory cytokinesCell subsetsCostimulatory moleculesTNF-alphaT cellsInflammatory stimuliDiabetesTransgenic miceCD4
2003
Accelerated Diabetes in Rat Insulin Promoter-Tumor Necrosis Factor-α Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules
Rajagopalan G, Kudva YC, Flavell RA, David CS. Accelerated Diabetes in Rat Insulin Promoter-Tumor Necrosis Factor-α Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules. Diabetes 2003, 52: 342-347. PMID: 12540606, DOI: 10.2337/diabetes.52.2.342.Peer-Reviewed Original ResearchConceptsClass II moleculesNecrosis factorT cellsHLA class II associationsHuman type 1 diabetesMajor histocompatibility class II moleculesFunctional class II moleculesClass II associationsType 1 diabetesRat insulin promoterTumor necrosis factorLocal proinflammatory environmentIslets of LangerhansAccelerated diabetesNOD miceHLA-DQ8Proinflammatory environmentC57BL/6 miceTNF-alphaDiabetesDisease pathogenesisSignificant protectionMajor histocompatibility complex locusNeonatal expressionMice
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
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